Differential Expression Of TREM-1 In Myelogenous Leukemia Cells

Abstract Objectives Triggering receptor expressed on myeloid cells (TREM) -1 is a receptor as a member of the immunoglobulin superfamily expressed on the cell-surface of neutrophils, monocytes and macrophages. This receptor amplifies the inflammatory response, activating the signaling pathway. TREM-1 expression is associated with mature myeloid cell development. TREM-1 is shed from the membrane of activated macrophages without the transmembrane and intracellular domains, and can be found as soluble TREM (sTREM)-1. Soluble TREM-1 is thought to negatively regulate TREM receptor signaling. Some studies currently reported that TREM-1 regulates the malignant behavior of cancer cells in lung cancer and HCC. However, no related studies about the role of TREM-1 in leukemia have been carried out. The aims of this study was investigated the TREM-1 expression in myelogenous leukemia cells. Methods Thirty-five patients with AML, twenty-five patients with CML and a control group of eleven healthy people were subjected to the study. TREM-1 expressions on the surfaces of leukemia cells were measured by flow cytometry. Plasma sTREM-1 levels were measured by ELISA. Results In this study, our results provide the first evidence that TREM-1 was differentially expressed in myelogenous leukemia cells. The TREM-1 mean ratio of median fluorescence intensity (mean ratio of MFI) was 3.13±0.88 and 2.52±0.40 in CML and AML patients, respectively. The TREM-1 mean ratio of MFI was 3.03±1.40 in myelogenous leukemia cell lines (K562, HL60, THP-1). The TREM-1 mean ratio of MFI was 5.37±0.88 in healthy controls. Compared to healthy controls, myelogenous leukemia cells had decreased TREM-1 expressions (P<0.001). The TREM-1 mean ratio of MFI was 4.89±0.60 in patients who are in complete remission after Novartis's Gleevec therapy. Compared with CML patient groups, patients who are in complete remission after Gleevec therapy had rising TREM-1 expressions (P<0.01). TREM-1 expressions of patients who are in complete remission after Gleevec therapy were slightly lower than the healthy controls, but this did not reach significance. No significant difference in TREM-1 expressions was seen between AML and CML patient groups, male and female patient groups, and cells derived from peripheral blood and bone marrow of the same leukemia patients (p>0.1). In addition, the plasma sTREM-1 levels were measured by ELISA. sTREM-1 levels was 48.54±57.63pg/mL for AML group and 43.72±23.93pg/mL for CML group. Results indicated that plasma sTREM-1 levels significantly higher in AML and CML patients than that in healthy controls (P<0.01). However, there was no significant difference in plasma sTREM-1 levels observed in AML patient group compared with CML patient group, male patients group compared with female patients group, and plasma from peripheral blood compared with plasma from bone marrow of the same leukemia patients (p>0.1). An ongoing project focuses on the relationship between the function of TREM-1 and occurrence, progression and prognosis of myelogenous leukemia, advances will be reported in time. Conclusion TREM-1 expression on leukemia cells was significantly lower in patients with AML and CML than those in healthy controls and patients in complete remission had increased TREM-1 expression. Patients with AML and CML had increased plasma soluble TREM-1. The TREM-1 expression on leukemia cells had an inverse correlation with plasma sTREM-1 level in AML and CML patients. Disclosures: No relevant conflicts of interest to declare.

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Pro- and Antiapoptotic Proteins Expression on Bone Marrow and Peripheral Blood CD34+Cells in Acute Leukemia (AL) Patients

Blood ◽

10.1182/blood.v118.21.4996.4996 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4996-4996

Author(s):

Elena E. Khodunova ◽

Elena N Parovichnikova ◽

Irina V. Galtzeva ◽

Sergey M. Kulikov ◽

Valeri G Savchenko

Keyword(s):

Bone Marrow ◽

Peripheral Blood ◽

Conflicts Of Interest ◽

Expression Level ◽

Leukemia Cells ◽

Control Group ◽

Healthy Donors ◽

Cd34 Cells ◽

Significant Difference ◽

Blast Cells

Abstract Abstract 4996 It was shown that drug resistance, poor-risk cytogenetics and poor prognosis in AL is associated with high level of Bcl-2 expression and low Bax/Bcl-2 ratio (<0,3). Fas-antigen (CD95) as a protein triggering the extrinsic apoptotic pathway is differently expressed on hematopoietic precursors. More immature CD34+/CD38- AML blast cells have lower expression of Fas/Fas-L and lower Fas-induced apoptosis than CD34+/CD38+cells. CD34+/CD38− leukemia precursors also have a reduced sensitivity to daunorubicin in vitro and increased expression of multidrug resistance genes (mrp/lrp). CD34+ leukemia cells have not yet been properly characterized regarding the expression of angiotensin converting enzyme (ACE) which regulatory influence on hematopoiesis is now beeing extensively investigated. ACE expression on blast cells is high, but it's still unknown how CD34+ACE+ leukemia cells behave after chemotherapy. Recent publications indicate that CD34+ACE+ hematopoietic precursors transplanted into NOD/SCID mice contribute 10-fold higher numbers of multilineage blood cells than their CD34+ACE- counterparts. We have studied the dynamics of Bcl-2, Bax, CD95 and ACE expression on CD34+ cells in peripheral blood (PB) and bone marrow (BM) in AL pts during treatment. PB and BM samples were collected before and on +36 day after chemotherapy. The antigens were detected by flow cytometry using monoclonal antibodies. We calculated 10 000 cells in each sample. 19 pts were included in the study: 10 - AML and 9 - ALL. The control group comprised 8 healthy donors. At time of diagnosis there were 40±5,7% of CD34+ cells in BM and 26±4,9% - in PB. There was no significant difference between AML and ALL. CD34+ cells in BM and PB of healthy donors constituted 1,6% and 0,27%, respectively. After induction therapy (+36 day) CD34+ cells decreased in BM to 6,1%±3,3 (p=0,0001), in PB to 3,7%± 2,7 (p=0,0008) in all pts. The data on antigens expression on CD34+ cells of BM and PB are presented in table 1 CD34+/Bcl-2+ CD34+/Bax+ CD34+/CD95+ CD34+/ACE+ BM PB BM PB BM PB BM PB AML pts n=10 0 day 38±11,6* 41±14 24,4±7,9 29,2±7,6* 16,4±8,5 23,2±7,8 21,7±9,5 20,8±8,7* 36 day 13,5±3,4** 23,7±5** 46,2±11,5 50,3±11 19,9±5,5 36,4±10 34±6,6 35±9,2** ALL pts n=9 0 day 36±11 33,7±12 46,2±9,4 37,4±3,7* 3,4±1,1* 7,1±2,5* 41±10,9 33,2±9,7* 36 day 18,4±5,8 26±8,9 38±11,8 40,5±10 26,2±9,1** 40,9±9,2** 34±10 62,8±10** Donors n=8 11,7±1,6 26,1±5,9 22,8±4 67,8±6,7 13,4±3,2 47,7±11,6 28±5,3 68,2±10,2 * − p<0.05 compare with donors ** − p<0.05 compare with day 0 CD34/Bcl-2 expression in BM in AML pts is significantly higher (p=0,04) at the diagnosis comparing with donors. CD34/Bcl-2 expression in PB in AML pts and in BM and PB in ALL pts is higher too, but not significantly. This expression level decreased substantially in BM and PB in AML pts on +36 day comparing with day 0 (p<0,05). We did not found significant changes in ALL pts. CD34/Bax expression in PB is significantly lower (p=0,003) both in AML and ALL pts in comparison with donors. In AML, not in ALL, chemotherapy caused augmentation of Bax expression in CD34+ BM and PB cells on +36 day. BM and PB CD34+ cells in donors had different expression characteristics of Bcl-2 and Bax, demonstrating much higher level of pro- and antiapoptotic markers in PB cells. On the contrast CD34+ leukemia cells in BM and PB had similar characteristics regarding CD34/Bcl-2 and CD34/Bax expression. This fact demonstrates the heterogeneity of donor CD34+cells in BM and PB and points that leukemia CD34+cells in BM and PB are rather similar. CD95 expression on CD34+ BM and PB before treatment is significantly lower (p=0,01, p=0,008) in ALL pts in comparison with donors, and this expression level increased after chemotherapy (p<0,05). CD34/CD95 expression in AML pts is similar with donors, and we didn't find changes after treatment. CD34/ACE coexpression in BM cells of leukemia pts and donors did not differ much at any time of evaluation. But CD34/ACE expression in PB cells of AML and ALL pts was much lower (p<0,05) than in donors and substantially increased on the day 36. So, our data demonstrate that Bcl-2, Bax, CD95 and ACE expression on CD34+ cells in AL pts and donors significantly differs. The chemotherapy provokes critical changes in CD34/CD95 expression in BM and PB in ALL pts, CD34/Bcl-2 expression in AML pts and ÑÂ34/ACE expression in PB in all AL pts. Disclosures: No relevant conflicts of interest to declare.

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Clinical observations of bone marrow transfusion for promoting bone marrow reconstruction after chemotherapy for AIDS-related lymphoma

BMC Immunology ◽

10.1186/s12865-021-00399-8 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Yixuan Liu ◽

Suhong Xie ◽

Lei Li ◽

Yanhui Si ◽

Weiwei Zhang ◽

...

Keyword(s):

Bone Marrow ◽

Immune System ◽

T Lymphocytes ◽

Peripheral Blood ◽

Autologous Bone Marrow ◽

Control Group ◽

Peripheral Vein ◽

Significant Difference ◽

Autologous Bone ◽

Aids Related Lymphoma

Abstract Background This study investigates the effect of autologous bone marrow transfusion (BMT) on the reconstruction of both bone marrow and the immune system in patients with AIDS-related lymphoma (ARL). Methods A total of 32 patients with ARL participated in this study. Among them, 16 participants were treated with conventional surgery and chemotherapy (control group) and the remaining 16 patients were treated with chemotherapy followed by autologous bone marrow transfusion via a mesenteric vein (8 patients, ABM-MVI group) or a peripheral vein (8 patients, ABM-PI group). Subsequently, peripheral blood and lymphocyte data subsets were detected and documented in all patients. Results Before chemotherapy, no significant difference in indicators was observed between three groups of ARL patients. Unexpectedly, 2 weeks after the end of 6 courses of chemotherapy, the ABM-MVI group, and the ABM-PI group yielded an increased level of CD8+T lymphocytes, white blood cells (WBC), and platelet (PLT) in peripheral blood in comparison to the control group. Notably, the number of CD4+T lymphocytes in the ABM-PI group was significantly higher than that in the other two groups. Additionally, no significant difference in haemoglobin levels was observed before and after chemotherapy in both the ABM-MVI and ABM-PI groups, while haemoglobin levels in the control group decreased significantly following chemotherapy. Conclusions Autologous bone marrow transfusion after chemotherapy can promote the reconstruction of both bone marrow and the immune system. There was no significant difference in bone marrow recovery and reconstruction between the mesenteric vein transfusion group and the peripheral vein transfusion group.

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Pentoxifylline During Steroid Window At Induction To Remission Increases Apoptosis In Childhood Acute Lymphoblastic Leukemia

Blood ◽

10.1182/blood.v122.21.2623.2623 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2623-2623

Author(s):

Oscar Gonzalez-Ramella ◽

Jimenez-Lopez Xochiquetzatl ◽

Sergio Gallegos-Castorena ◽

Pablo Ortiz-Lazareno ◽

Jose Manuel Lerma-Diaz ◽

...

Keyword(s):

Bone Marrow ◽

Acute Lymphoblastic Leukemia ◽

Complete Remission ◽

Cancer Cells ◽

Lymphoblastic Leukemia ◽

Remission Induction ◽

Control Group ◽

Induction Phase ◽

Study Group ◽

Significant Difference

Abstract Introduction Acute lymphoblastic leukemia (ALL) is the most common cancer diagnostic in children, and it represents the second death cause in this population. Despite advances in the treatment of childhood ALL, there are small portion of patients whom still succumb to this disease. A reduced apoptosis in cells plays an important role in carcinogenesis. This phenomenon is an important component in the cytotoxicity induced by anticancer drugs. A currently challenge is the chemotherapy resistance of tumor cells, inhibiting the apoptosis induced by chemotherapy. Pentoxifylline, (PTX) has been studied for its role on increase of apoptosis on cancer cells by different pathways. Our group has reported its efficacy in vitro and ex vivo in increasing apoptosis induced by chemotherapy drugs such as adriamycin and cisplatin in fresh leukemic human cells, lymphoma murine models and cervical cancer cells. We conducted a phase 1 controlled randomized trial to evaluate the efficacy of adding PTX to the steroid window during the remission induction phase in new diagnosed children with ALL. Methods We included all children from both sexes from 9 months to 17 years old during October 2011 to December 2012. Patients were divided into 3 groups, the first one as a non-malignant control group (NL group) included children with a non-hematology disease in which bone marrow aspiration (BMA) was mandatory in order to reach the diagnosis. The second one, the ALL control group whom received prednisone (PRD group) for the steroid window at 40mg/m2/day PO from day -7 to day 0; and then the third one (PTX group), the study group which included children receiving the steroid phase with PRD as early described, plus PTX at 10mg/kg/day IV divided in 3 doses, at the same days as recommended in our treatment protocol (Total Therapy XV). For all 3 groups a BMA was performed at diagnosis, for PRD group as well as PTX group, a second BMA was also collected at day 0. Apoptosis was evaluated by means of Annexin V Apoptosis Detection Kit FITC/PI (eBioscience¨, San Diego, CA, USA) in 1×106 bone marrow mononuclear cells. We measured minimal residual disease (MRD) by flow cytometry at day 14 to demonstrate complete remission in leukemic patients. Statically analysis was performed by U Man Whitney. Results We enrolled 32 patients: 10 in NL group; 11 in PRD group; and 11 in PTX group. The median age of all groups was 6 years (range 9 months-17 years). In PRD group, patient 1 abandoned treatment after administration of day 0, nevertheless the second BMA sample was collected. Patient number 7 died at day 4 due to complications from tumor lysis syndrome. Consequently, in these patients we were not able to measure MRD and BM aspiration at day 14. Except one patient in PRD group, all achieved complete remission at day 14. We did not find any significant difference between NL group and PRD and PTX groups before intervention (U=32 p=0.7; U=28.5 p=0.48 respectively). There was no significant difference between treatment groups before intervention (U= 37 p=0.79). However, after treatment we found an important difference between PRD and PTX groups, we observed an increase in apoptosis in PTX group in comparison with PRD group (U=17.5 p=0.04). There were no adverse effects during treatment. Conclusions The present study is the first one that shows the efficacy of PTX in increasing apoptosis induced by PRD in new ALL diagnosed children, whom have not received any treatment yet. This might be helpful, not only in patients with relapse, but to increase the overall cure rate in ALL. Further studies are needed to prove this hypothesis. With this objective, our study group is already planning a second trial were PTX will be given during all remission induction phase. Experimental reports strongly suggest that PTX induces inhibition of the transcription factor NF-ĸB, by inhibiting survival gens and facilitating apoptosis. To prove it, we are currently processing these patients' samples to know their genetic expression. Disclosures: No relevant conflicts of interest to declare.

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Reduction of Tregs with Expansion of Th1 Cells and Lack of IFN-γ Secretion by GPI Negative T-Cells In PNH

Blood ◽

10.1182/blood.v116.21.2240.2240 ◽

2010 ◽

Vol 116 (21) ◽

pp. 2240-2240

Author(s):

Shahram Kordasti ◽

Modupe Elebute ◽

Pilar Perez Abellan ◽

Austin G Kulasekararaj ◽

Janet Hayden ◽

...

Keyword(s):

Bone Marrow ◽

T Cells ◽

High Resolution ◽

Peripheral Blood ◽

Clonal Expansion ◽

T Cell Subsets ◽

Th1 Cells ◽

Healthy Controls ◽

Significant Difference ◽

Ifn Γ

Abstract Abstract 2240 Introduction and Aim: Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired haematopoietic stem cell disorder characterized by intravascular haemolysis and thrombosis. The pathogenetic link with bone marrow failure syndromes is well recognized, however the process of clonal expansion of the glycosylphosphatidylinositol (GPI)-deficient cells over normal haemotopoiesis remains unclear. To further elucidate mechanisms leading to clonal expansion in PNH, we investigated the immunological profile and performed high-resolution genome-wide karyotyping using Affymetrix SNP6 microarrays. Patients and Methods: The percentage and absolute numbers of CD4+ and CD8+ T-cell subsets, NK cells and B cells in peripheral blood were assessed in 8 patients with PNH prior to any therapy and 8 healthy age matched controls. High resolution SNP6 karyotyping was performed on bone marrow (n=15) and peripheral blood (n=12) of these patients. Bone marrow from an additional 8 patients was enriched for CD34+59- and CD34+59+ cell fractions for SNP array karyotyping. Abberations that overlapped by >50% with variations found in the Database of Genomic Variants, as well as an internal series of 91 normal subjects were excluded from further analysis. T-cells were stimulated and then stained intracellularly for TNF-α and IFN-γ (Th1), IL-4 (Th2) and IL-17 (Th17). NK cells were defined as CD3– CD56+. B cells were defined as CD3-CD19+. CD3+ CD4+ T-cell subsets were defined as CD45RO–CD27+ naïve, CD45RO+ CD27+ CD62L+ central memory, CD45RO+ CD27+ CD62L– effector memory, CD45RO+CD27– effectors and CD45RO–CD27– terminal effectors. CD4+ Tregs were defined as CD3+CD4+ CD25high CD27+Foxp3+. Results: There were no significant differences in the number or percentage of different CD8+ and CD4+ T-cells compared to healthy controls except for the number of Tregs and Th1 cells. In our cohort of patients, the number of Th1 cells was significantly higher than healthy controls (4.1×107/L v 0.93 × 107/L, p=0.039), whereas the number of Tregs cells was lower (0.75 × 107/L v 1.36 × 107/L, p=0.028). There was no significant difference in the number of Th2 and Th17 cells between patient and healthy subjects. Within CD4+ T-cells two distinct CD59+ and CD59- populations were identified, of which the CD59- cells were unable to secrete IFN-γ in response to stimulation compared to CD59+ population. On average 48% of CD4+ CD59+ T-cells secrete IFN-γ compared to 2% in the CD59- population. There was no significant difference in IL17 and IL4 secretion between CD59+ and CD59- T-cells. SNP karyotyping revealed three regions of uniparental disomy (UPD); UPD1p26.11-p34.3, UPD1p13.3-p13.1in one peripheral blood sample and UPD7q32.1-q34 in one bone marrow sample. There were no additional somatic genomic aberrations detected in any of the samples. Of note, purified CD34+59- cells did not reveal any clonal copy number changes or regions of UPD. Conclusion: Specific analysis of Xp22.1 did not reveal any aberrations of the PIGA gene, suggesting aberrations of the PIGA gene may be restricted to mutations or epigenetic abnormalities. Our immunological profiling revealed an expansion of Th1 cells and diminished Tregs in the peripheral blood, which is in contrast to our published data from both MDS and AA patients. The lack of IFN-γ secretion by GPI deficient T-cells also suggests an additional immunological defect in these patients, which may contribute in disease pathogenesis. Disclosures: No relevant conflicts of interest to declare.

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HEMATOLOGICAL CHARACTERISTICS OF YEMENI ADULTS AND CHILDREN WITH VISCERAL LEISHMANIASIS. COULD EOSINOPENIA BE A SUSPICION INDEX?

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2017.056 ◽

2017 ◽

Vol 9 (1) ◽

pp. 2017056 ◽

Cited By ~ 3

Author(s):

Jameel Al-Ghazaly ◽

Waled Al-Dubai ◽

Munasser Abdullah ◽

Leila Al-Gharasi

Keyword(s):

Bone Marrow ◽

Visceral Leishmaniasis ◽

Peripheral Blood ◽

Bone Marrow Aspiration ◽

Bone Marrow Examination ◽

Control Group ◽

Significant Difference ◽

Adults And Children ◽

Frequent Accompaniment ◽

Suspicion Index

Background and objectives: Delay in the diagnosis of visceral leishmaniasis (VL) particularly in non-endemic areas is associated with higher mortality. In our experience, we found that marked bone marrow eosinopenia was a very frequent accompaniment of VL and might be a useful clue for the diagnosis, which indicates the opportunity for further morphological assessment. The aim of this study was to describe the hematological characteristics including peripheral blood and bone marrow findings of Yemeni adults and children with VL.Methods: We conducted a descriptive analytic study to evaluate systematically peripheral blood and bone marrow findings of Yemeni adults and children with VL. Peripheral blood and bone marrow aspiration of patients with bone marrow aspirate confirmed VL were examined. Forty-seven patients with the main age (±SD) of 17.34±11.37 years (Range: 1-60) were included in the study. Fifty-one non-VL subjects with splenomegaly and pancytopenia or bicytopenia served as control group.Results: All patients with VL had anemia, 41 (87%) leukopenia, 42 (89%) neutropenia, 44 (94%) thrombocytopenia, 42 (89%) eosinopenia, 34 (72%) pancytopenia and 13 (28%) had bicytopenia. In bone marrow examination 40 (85%) showed hypercellularity, 44 (94%) eosinopenia, 24 (51%) dyserythropoiesis, 22 (47%) lymphocytosis, 8 (17%) plasmacytosis, 27 (57%) decreased iron stores and 20 (43%) showed decreased sideroblasts. Comparison of VL patients with the control group showed significantly more frequent peripheral blood eosinopenia and lymphopenia and marrow eosinopenia. There was no significant difference between adults and children in any of the hematological features.Conclusion: Anemia, leukopenia, neutropenia, thrombocytopenia, eosinopenia, pancytopenia and marked bone marrow eosinopenia were the most common findings. The finding of marked bone marrow eosinopenia is a significant clue for the diagnosis of visceral leishmaniasis in patients who present with splenomegaly associated with cytopenias. This finding is particularly valuable in non-endemic areas.Keywords: Visceral Leishmaniasis, Yemen, Early Diagnosis, Hematological Features, Bone Marrow Eosinopenia.

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Reductive regulation of BECN1 gene in adult Egyptian patients with do novo AML

Egyptian Journal of Medical Human Genetics ◽

10.1186/s43042-020-00087-z ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Manal Fawzy Ghozlan ◽

Botheina Ahmed Thabet Farweez ◽

Nesma Ahmed Safwat ◽

Noha Bassiouny Hassan ◽

Walaa Ali Elsalakawy

Keyword(s):

Gene Expression ◽

Bone Marrow ◽

Peripheral Blood ◽

De Novo ◽

Quantitative Polymerase Chain Reaction ◽

Control Group ◽

Significant Difference ◽

Egyptian Patients ◽

Blast Cells ◽

De Novo Aml

Abstract Background Acute myeloid leukaemia (AML) is a clonal haematopoietic disease characterized by the proliferation of immature blast cells in the bone marrow and peripheral blood. Autophagy is an inherent cellular route by which waste macromolecules are engulfed within autophagosomes prior to their fusion with cytoplasmic lysosomes for degradation. The BECN1 gene encodes the Beclin-1 protein, which regulates autophagy. Few reports have investigated BECN1 gene expression and its value in AML patients. Results This randomized case-control study included 50 newly diagnosed AML patients, in addition to 20 subjects as a control group. BECN1 gene expression was assessed using real-time quantitative polymerase chain reaction (qRT-PCR). The median level of BECN1 gene expression in AML patients was 0.41 (IQR 0.29–1.03) in comparison to 1.12 (IQR 0.93–1.26) in the control group (P = 0.000). Seventy-two percent of AML patients showed reduced BECN1 gene expression, which was highly significantly associated with intermediate and adverse cytogenetic risk. Reduced BECN1 gene expression was associated with older age, higher total leukocyte counts, the presence of peripheral blood blast cells, a higher percentage of bone marrow blast cells, and higher expression of CD34 and CD117. FLT3-ITD mutation was detected in 14 patients (38.9%), all of whom showed reduced BECN1 gene expression (P = 0.006). BECN1 gene expression was also reduced in non-responder AML patients, with a highly statistically significant difference (P = 0.002). Conclusion A reduction in BECN1 gene expression might indicate a poor prognosis in adult Egyptian patients with de novo AML. Decreased BECN1 gene expression is associated with a higher risk of resistance to treatment. Targeting autophagy pathways may help in the treatment of AML patients.

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The Criteria for Bone Marrow Recovery Post–Myelosuppressive Therapy for Acute Myelogenous Leukemia: A Quantitative Study

Archives of Pathology & Laboratory Medicine ◽

10.5858/2007-131-1281-tcfbmr ◽

2007 ◽

Vol 131 (8) ◽

pp. 1281-1289

Author(s):

Farah Khalil ◽

Hernani Cualing ◽

Julia Cogburn ◽

Lili Miles

Keyword(s):

Bone Marrow ◽

Peripheral Blood ◽

Acute Myelogenous Leukemia ◽

Recovery Period ◽

Myelogenous Leukemia ◽

Control Group ◽

Allogeneic Bone ◽

Bone Marrow Biopsies ◽

Acute Myelogenous ◽

Rate Of Recovery

Abstract Context.—Although the early post–myelosuppressive chemotherapy pathologic changes of the marrow have been described, the rate and the histologic definition of recovery are not defined. Objective.—To study the rate of recovery of bone marrow in patients given myelosuppressive therapy for acute myelogenous leukemia, establish the histologic criteria of recovered marrow, and correlate the recovery pattern with those patients who received a bone marrow transplant by using histology, peripheral blood, immunophenotyping, and computerized morphometry and mathematical slope equation. Design.—We studied the post–myelosuppression recovery of the bone marrow to determine patterns and rate of recovery in 135 serial bone marrow biopsies of 51 patients. These patients were divided into 2 groups: 1 group of 28 cases diagnosed with acute myeloid leukemia, the majority treated with cytarabine (Ara-C) infusion for 7 days and daunorubicin intravenously daily for 3 days (7+3 regimen), and the other control group of 23 cases treated with chemotherapy or allogeneic bone marrow transplantation for a variety of hematologic malignancies. All biopsies during the recovery period were obtained before consolidation regimen. We used morphometry to calculate the cellularity and myeloid to erythroid ratio and quantified megakaryocytes CD10 versus time from day 14 onward. The absolute neutrophil and platelet counts for 28 cases were related to histologic recovery. Results.—From day 14, we noted a differential slope of recovery of these patients with no difference in male and female patients, P = .45, but a difference between younger and older patients (>58.5 years), P = .03. After regenerative hyperplasia, the cellularity plateaus, the myeloid to erythroid ratio, and the megakaryocytes even out with platelet normalization, and the early CD10+ B cells rise from day 40 onward, P = .01. The patterns of recovery after day 60 of postchemotherapy and posttransplantation patients are similar. Complete histologic and peripheral blood recovery is noted at day 38 and thereafter. Conclusions.—By linear equation using at least 2 trephine biopsy specimens, the projected rate of cellular recovery may be determined, and 5 histologic features are associated with complete histologic recovery.

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Expression of BECN1 gene in Acute Myeloid Leukemia: Association with Hematological and Clinical Parameters

QJM ◽

10.1093/qjmed/hcab091.007 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Mohamed Moustafa Ahmed ◽

Manal Fawzy Ghozlan ◽

Walaa Ali Mohamed ◽

Nesma Ahmed Safwat ◽

Noha Bassiouny Hassan

Keyword(s):

Gene Expression ◽

Bone Marrow ◽

Acute Myeloid Leukemia ◽

Peripheral Blood ◽

Myeloid Leukemia ◽

Control Group ◽

Fish Analysis ◽

Newly Diagnosed ◽

Significant Difference ◽

Acute Myeloid

Abstract Background In acute myeloid leukemia (AML), there is copy number loss in autophagic genes such as BECN1. Accordingly, decreased autophagy and the development of AML are related. BECN1 is a critical mediator that influences the onset and progress of autophagy. Objective To investigate the expression status of BECN1 gene in newly diagnosed adult AML patients and its association with various hematological parameters and clinical outcomes. Methods Case control study to study BECN1 gene expression variability between 50 newly diagnosed adult AML patients and 20 healthy age and sex matched controls, with follow up of the patients to detect its effect on induction therapy. All AML patients underwent full history taking, through clinical examination, laboratory investigations such as complete blood count (CBC) with examination of peripheral blood and bone marrow Leishman stained films, immunophenotyping, cytogenetic analysis (karyotyping/FISH analysis) and BECN1 gene expression analysis using real-time quantitative polymerase chain reaction (qRT-PCR). Results In our study, a highly significant difference was found as regards reduced expression of BECN1 gene in patients group compared to control group. We also found reduced BECN1 gene expression in both intermediate and adverse risk groups compared to favorable risk group. Reduced expression of BECN1 gene was associated with increasing age and total leukocytic count (TLC), peripheral blood (PB) and bone marrow (BM) blasts, the presence of FLT3-ITD mutation, CD34 and CD117 and in non-responders group. No statistically significant difference was found as regards haemoglobin (Hb) level, platelet (PLT) count and FAB subtypes. Conclusion Autophagy plays an important role in the pathogenesis of AML. Furthermore; the reductive regulation of the BECN1 gene may carry a poor prognosis and is associated with many well established bad prognostic factors especially FLT3-ITD mutation. Targeting autophagy pathways especially its major regulator (BECN1 gene) may become an effective and promising new line of therapy for AML patients.

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Elevated Serum Neutrophil Elastase but Not Proteinase 3 Is Present in Patients with Myeloid Leukemia.

Blood ◽

10.1182/blood.v108.11.4430.4430 ◽

2006 ◽

Vol 108 (11) ◽

pp. 4430-4430

Author(s):

Anna Sergeeva ◽

Yoko Ono ◽

Jeffrey J. Molldrem

Keyword(s):

Bone Marrow ◽

Neutrophil Elastase ◽

Myeloid Leukemia ◽

Elevated Serum ◽

Myelogenous Leukemia ◽

Leukemia Cells ◽

Control Group ◽

Proteinase 3 ◽

Gm Csf ◽

Healthy Donors

Abstract Proteinase 3 (P3) and neutrophil elastase (NE) are abnormally expressed in the cytoplasm of myeloid leukemia, and we have shown that the HLA-A2-restricted peptide PR1 is processed and cross-presented from both proteins by antigen-presenting cells (APC) to cytotoxic T lymphocytes (CTL). PR1-specific CTL kills leukemia cells and contributes to cytogenetic remission in patients with chronic myelogenous leukemia. Both exogenous P3 and NE can bind to monocytes and P3 promotes DC maturation in vitro. Since high levels of circulating P3 were found in patients with the ANCA-associated systemic vasculitis Wegener’s granulomatosis, modulation of DC by P3 has been implicated in reversal of tolerance. The role of extracellular P3 and NE in reversing tolerance in patients with myeloid leukemia is unknown. We used an ELISA assay to assess P3 and NE level in the sera of patients with AML and CML. Serum NE level was highly increased in all 15 AML patients studied (1045±149 ng/ml, n = 15) and in all 15 CML patients (1013±128, n = 15), compared to a control group of healthy donors (54±13 ng/ml, n = 4; p = 0.0038 and p = 0.0014, respectively). In contrast, serum P3 was increased in only 5 out of 18 (28%) AML patients (47 ± 18, n = 18 ng/ml) and in 8 out of 28 (29%) CML patients (95 ± 44 ng/ml, n = 28) compared to a group of 14 healthy donors (10 ± 2.2 ng/ml; p = 0.09 and p = 0.06, respectively). There was no relationship between elevated serum NE and P3 levels (r=0.16, n=35). P3 level in untreated patients and healthy donors did not change within at least 13 months, although P3 decreased after allogeneic BMT in 5 out of 5 patients (p < 0.05) with high serum levels of P3 pre-BMT. Because P3 is expressed by myeloid progenitor cells in the bone marrow, we studied the concentration of P3 in bone marrow-derived serum (BMS). To our surprise, BMS P3 concentration in patients with myeloid leukemia (23 ± 9.5 ng/ml, n = 9) was similar to that of a control group of patients with non-myeloid hematological malignancies (27 ± 11.8, n = 5) (p = 0.08), and BMS P3 concentration was similar to sera P3 concentration in the same patient (p = 0.52). Interestingly, BMS P3 level correlated with the level of BMS GM-CSF (quantified by ELISA) in a small group of patients with AML and CML (r = 0.94, n = 9), suggesting that P3 secretion by leukemia cells may be downstream of GM-CSF. We also analyzed membrane expression of P3 and NE in 5 AML patients using flow cytometry and found that P3, but not NE, was expressed on circulating cells in 3 of 5 patients. This unique expression of P3 and NE suggests that circulating NE might be the predominant source of cross-presented PR1 antigen by APC or myeloid leukemia cells.

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The prognostic importance of neutrophil-to-lymphocyte ratio in testicular cancer

Urologia Journal ◽

10.1177/0391560321993584 ◽

2021 ◽

pp. 039156032199358

Author(s):

Ahmet Arıman ◽

Erkan Merder

Keyword(s):

Testicular Cancer ◽

Patient Group ◽

Peripheral Blood ◽

Control Group ◽

Neutrophil Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

Significant Difference ◽

Prognostic Groups ◽

Radical Orchiectomy ◽

Prognostic Importance

Purpose: Testicular cancer is mostly seen in young men. We planned this study that neutrophil-lymphocyte ratio (NLR) would help us predict the prognosis of the patients, except known markers such as AFP, hCG, and LDH. Patients and Method: Between 2015 and 2020, we conducted our study on 152 patients undergoing radical orchiectomy in our clinic. We divided our patients into good, moderate, and poor prognostic groups. We also created a control group of healthy patients of similar ages. We evaluated the NLR results in preoperative peripheral blood statistically among these groups. Results: We found a significant difference between the control group and the patient group, and between the good and moderate/poor prognostic groups for preoperative NLR. Conclusion: This study created the opinion that preoperative NLR will help us predict the prognosis of patients.

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