TREATMENT OF ACUTE LEUKEMIA

PEDIATRICS ◽  
1956 ◽  
Vol 18 (4) ◽  
pp. 643-660
Author(s):  
Joseph H. Burchenal ◽  
M. Lois Murphy ◽  
Charlotte T. C. Tan
Keyword(s):  
Bone Marrow ◽  
Acute Leukemia ◽  
Leukocyte Count ◽  
Bone Marrow Aspiration ◽  
Blood Lead ◽  
Leukemic Cells ◽  
Total Leukocyte Count ◽  
Differential Leukocyte Count ◽  
Complete Replacement ◽  
Susceptibility To Infection

IN TREATMENT of acute leukemia in children, as in treatment of any form of cancer, early diagnosis is of great importance. Although in contrast to many other tumors in children, leukemia is never curable even when detected at the early stages, the sooner treatment can be initiated, the more chance there is of having sufficient time to achieve a beneficial effect. The most important single factor in making the diagnosis of leukemia is a high degree of suspicion. Patients with pains in the bones and joints, with any hemorrhagic tendency, with increased susceptibility to infection or with an unexplained anemia or fever should have an immediate determination of total and differential leukocyte count, hemoglobin, and platelets. If any abnormality is found or if the symptoms persist, a bone marrow aspiration is essential. If these procedures are utilized, it is the rare case in which the diagnosis cannot be made with relative ease. In most cases of acute leukemia, there is almost complete replacement of the normal elements in the marrow by leukemic cells. Depression or absence of erythropoietic activity in the marrow and possibly decreased life span of the circulating erythrocytes leads to severe anemia with the accompanying symptoms of pallor, easy fatigability, and dyspnea on exertion. The decreased megakaryocytic activity in the bone marrow and the decrease of platelets in the circulating blood lead to petechiae, ecchymoses, and other hemorrhagic manifestations. In the peripheral blood the total leukocyte count may be high, normal, or low but, as most of the cells are abnormal in type, the patient is less able to combat infection.

scholarly journals Mixed Phenotype Acute Leukemia Presenting as Leukemia Cutis

2016 ◽  
Vol 2016 ◽  
pp. 1-3 ◽  
Author(s):  
Geetha Narayanan ◽  
M. T. Sugeeth ◽  
Lali V. Soman
Keyword(s):  
Bone Marrow ◽  
Acute Leukemia ◽  
Bone Marrow Aspiration ◽  
Skin Lesions ◽  
The Body ◽  
Leukemic Cells ◽  
Monocytic Differentiation ◽  
Cutaneous Lesions ◽  
Congenital Leukemia ◽  
Leukemia Cutis

Leukemia cutis (LC) is defined as infiltration of the skin by leukemic cells resulting in clinically recognizable cutaneous lesions. It is common in congenital leukemia and acute myeloid leukemia. However, LC has rarely been reported with mixed phenotypic acute leukemia (MPAL). We report the case of a lady who presented with erythematous papular and nodular lesions all over the body. Skin biopsy showed leukemic infiltration and bone marrow aspiration showed MPAL of the T/myeloid with monocytic differentiation lineage. This is the first report of an adult patient with MPAL of the T/myeloid with monocytic differentiation type presenting with leukemia cutis. She was started on chemotherapy with Hyper-CVAD. There is complete resolution of the skin lesions and she has achieved bone marrow remission after the first cycle of chemotherapy.

scholarly journals Peripheral blood and bone marrow responses under stress of cypermethrin in albino rats

2014 ◽  
Vol 7 (1) ◽  
pp. 33-40 ◽  
Author(s):  
Sunita Pande ◽  
Prabhu Narain Saxena ◽  
Brijender Bhushan ◽  
Nishi Saxena
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Leukocyte Count ◽  
Haemoglobin Concentration ◽  
Total Leukocyte Count ◽  
Albino Rats ◽  
Differential Leukocyte Count ◽  
Corpuscular Haemoglobin ◽  
Mean Corpuscular Haemoglobin ◽  
Rbc Count

Abstract Pyrethroids, commercially available pesticides, are greatly in use these days, and thus they carry considerable chances of contaminating various ecosystems. Haematotoxicity of cypermethrin, a broadly used type II pyrethroid, has been assessed in the present study. Selected parameters included determination of total RBC count, haemoglobin concentration (Hb conc.), packed cell volume (PCV), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), erythrocyte sedimentation rate (ESR), total leukocyte count (TLC), differential leukocyte count (DLC), along with qualitative analysis of blood and bone marrow. Of these parameters, those showing significant decline following cypermethrin intoxication included total RBC count, Hb conc., PCV, MCV, MCH, whereas non-significant decrease was observed in the case of MCHC. ESR, TLC and DLC, on the other hand, increased significantly following cypermethrin intoxication. Qualitative changes included altered red cell morphology such as microcystosis, appearance of stomatocytes, poikilocytosis, giant platelet formation, etc. in peripheral blood and increased erythroid precursors in bone marrow of treated rats. These parameters were however normalised following twenty-two days of recovery phase

scholarly journals Immune function during pregnancy varies between ecologically distinct populations

2020 ◽  
Vol 2020 (1) ◽  
pp. 114-128
Author(s):  
Carmen Hové ◽  
Benjamin C Trumble ◽  
Amy S Anderson ◽  
Jonathan Stieglitz ◽  
Hillard Kaplan ◽  
...  
Keyword(s):  
Leukocyte Count ◽  
Total Leukocyte Count ◽  
Future Research ◽  
Differential Leukocyte Count ◽  
Ecological Conditions ◽  
Trade Offs ◽  
The Usa ◽  
Immunological Changes ◽  
Fetal Antigens ◽  
Pathogen Exposure

Abstract Background and objectives Among placental mammals, females undergo immunological shifts during pregnancy to accommodate the fetus (i.e. fetal tolerance). Fetal tolerance has primarily been characterized within post-industrial populations experiencing evolutionarily novel conditions (e.g. reduced pathogen exposure), which may shape maternal response to fetal antigens. This study investigates how ecological conditions affect maternal immune status during pregnancy by comparing the direction and magnitude of immunological changes associated with each trimester among the Tsimane (a subsistence population subjected to high pathogen load) and women in the USA. Methodology Data from the Tsimane Health and Life History Project (N = 935) and the National Health and Nutrition Examination Survey (N = 1395) were used to estimate population-specific effects of trimester on differential leukocyte count and C-reactive protein (CRP), a marker of systemic inflammation. Results In both populations, pregnancy was associated with increased neutrophil prevalence, reduced lymphocyte and eosinophil count and elevated CRP. Compared to their US counterparts, pregnant Tsimane women exhibited elevated lymphocyte and eosinophil counts, fewer neutrophils and monocytes and lower CRP. Total leukocyte count remained high and unchanged among pregnant Tsimane women while pregnant US women exhibited substantially elevated counts, resulting in overlapping leukocyte prevalence among all third-trimester individuals. Conclusions and implications Our findings indicate that ecological conditions shape non-pregnant immune baselines and the magnitude of immunological shifts during pregnancy via developmental constraints and current trade-offs. Future research should investigate how such flexibility impacts maternal health and disease susceptibility, particularly the degree to which chronic pathogen exposure might dampen inflammatory response to fetal antigens. Lay Summary This study compares immunological changes associated with pregnancy between the Tsimane (an Amazonian subsistence population) and individuals in the USA. Results suggest that while pregnancy enhances non-specific defenses and dampens both antigen-specific immunity and parasite/allergy response, ecological conditions strongly influence immune baselines and the magnitude of shifts during gestation.

scholarly journals Expression of the three myeloid cell-associated immunoglobulin G Fc receptors defined by murine monoclonal antibodies on normal bone marrow and acute leukemia cells

Blood ◽  
1989 ◽  
Vol 73 (7) ◽  
pp. 1951-1956
Author(s):  
ED Ball ◽  
J McDermott ◽  
JD Griffin ◽  
FR Davey ◽  
R Davis ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Monoclonal Antibodies ◽  
Acute Leukemia ◽  
Cell Sorting ◽  
Lymphoblastic Leukemia ◽  
Mononuclear Phagocytes ◽  
Leukemic Cells ◽  
Leukemia Cells ◽  
Normal Bone Marrow ◽  
Normal Bone

Monoclonal antibodies (MoAbs) have been prepared recently that recognize the three cell-surface receptors for the Fc portion of immunoglobulin (Ig), termed Fc gamma RI (MoAb 32.2), Fc gamma R II (MoAb IV-3), and Fc gamma R III (MoAb 3G8) that are expressed on selected subsets of non-T lymphocyte peripheral blood leukocytes. In the blood, Fc gamma R I is expressed exclusively on monocytes and macrophages, Fc gamma R II on granulocytes, mononuclear phagocytes, platelets, and B cells, and Fc gamma R III on granulocytes and natural killer (NK) cells. We have examined the expression of these molecules on normal bone marrow (BM) cells and on leukemia cells from the blood and/or BM in order to determine their normal ontogeny as well as their distribution on leukemic cells. BM was obtained from six normal volunteers and from 170 patients with newly diagnosed acute leukemia. Normal BM cells were found to express Fc gamma R I, II, and III with the following percentages: 40%, 58%, and 56%, respectively. Cell sorting revealed that both Fc gamma R I and Fc gamma R II were detectable on all subclasses of myeloid precursors as early as myeloblasts. Cell sorting experiments revealed that 66% of the granulocyte-monocyte colony-forming cells (CFU-GM) and 50% of erythroid burst-forming units (BFU-E) were Fc gamma R II positive with only 20% and 28%, respectively, of CFU-GM and BFU-E were Fc gamma R I positive. Acute myeloid leukemia (AML) cells expressed the three receptors with the following frequency (n = 146): Fc gamma R I, 58%; Fc gamma R II, 67%; and Fc gamma R III, 26% of patients. Despite the fact that Fc gamma R I is only expressed on monocytes among blood cells, AML cells without monocytoid differentiation (French-American-British [FAB]M1, M2, M3, M6) were sometimes positive for this receptor. However, Fc gamma R I was highly correlated with FAB M4 and M5 morphology (P less than .001). Fc gamma R II was also correlated with FAB M4 and M5 morphology (P = .003). Cells from 11 patients with acute lymphoblastic leukemia were negative for Fc gamma R I, but six cases were positive for Fc gamma R II and III (not the same patients). These studies demonstrate that Ig Fc gamma R are acquired during normal differentiation in the BM at or before the level of colony-forming units. In addition, we show that acute leukemia cells commonly express Fc gamma R.

scholarly journals TO DETERMINE THE FREQUENCY OF VISCERAL LEISHMANIASIS IN PERIPHERAL CYTOPENIC PATIENT IN PATHOLOGY DEPARTMENT HAYATABAD MEDICAL COMPLEX.

1969 ◽  
Vol 4 (2) ◽  
pp. 560-566
Author(s):  
ZARD ALI KHAN ◽  
MOHAMMAD SAJJAD ◽  
IMRAN UD DIN ◽  
MUKAMIL SHAH ◽  
SHAH JEHAN
Keyword(s):  
Bone Marrow ◽  
Visceral Leishmaniasis ◽  
Case Series ◽  
Bone Marrow Aspiration ◽  
Bone Marrow Examination ◽  
Total Leukocyte Count ◽  
Full Blood Count ◽  
Female Ratio ◽  
Pathology Department ◽  
Case Series Study

BACKGROUND: Visceral Leishmaniasis is a chronic disease and was first described in 1903, byLIESHMAN and DONOVAN. The disease is common in tropical and sub tropical areas of the worldwith various hematological manifestations. It is characterized by fever, visceromegaly, weight loss,pancytopenia and hypergammaglobulenemia. The disease is silent killer, invariably killing almost alluntreated patients, but curable with hematological improvement within 4-6 weeks of treatment.OBJECTIVE: To determine the frequency of Visceral Leishmaniasis in patints with cytopenias .MATERIAL AND METHODS: A descriptive study conducted in Pathology department, HayatabadMedical Complex, Hayatabad from September 1, 2012 to August 31, 2013. This study comprises of 126patients, subjected to complete blood counts. Diagnosis were confirmed by finding Amastigote( L/Dbody) from bonemarrow aspirate. All the patients who were referred to pathology Department of thehospital for bone marrow examination, with the results of peripheral blood using automatedHaematology analyzer, Sysmex KX 21 showing cytopenia were included in the study. Consent wastaken from the patient for bone-marrow aspiration procedure. After consent detailed history, physicalexamination was done.Laboratory investigations i.e. full blood count, which includes hemoglobin estimation, white blood cell,red blood, and platelet count.Bone marrow cytology (Giemsa stain) was recorded on the designed profroma.Posterior superior iliac spine (PSIS) was used as the site for aspiration in adults and children over 2years of ageRESULT: Descriptive case series study of 126 patients of peripheral cytopenia. In which 77 (61.1%)patients were males and 49 (38.9%) were female with male to female ratio of 1.57: 1 It was also foundin this study that visceral leishmaniasis was present in 29 (23%) of cases and the male: female were 1.6:1. Result of the automated hematology analyzer of peripheral cytopenic patients in visceralleishmaniasis show that all of the patients were having total leukocyte count less than 4000/cmm(100%). The hemoglobin level wass less than lOgm/dl in 26 cases (87.7%) and more than lOgm/dl inthree cases (10.3%). In case of platelets count, 27 cases (93.1%) were having platelets count less than150000/cmm.CONCLUSION: Incidence of visceral leishmaniasis is highier in children age group 1-10 years, alsomales are more prone than females. Leukopenia is recorded in all (100%) of the cases, followed bythrombocytopenia (93.1%) and anemia (Hb <10gm %) 87.7% cases.KEY WORD: Visceral Leishmaniasis, Kala Azar, Amastigote (L/D body)

scholarly journals Expression of the three myeloid cell-associated immunoglobulin G Fc receptors defined by murine monoclonal antibodies on normal bone marrow and acute leukemia cells

Blood ◽  
1989 ◽  
Vol 73 (7) ◽  
pp. 1951-1956 ◽  
Author(s):  
ED Ball ◽  
J McDermott ◽  
JD Griffin ◽  
FR Davey ◽  
R Davis ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Monoclonal Antibodies ◽  
Acute Leukemia ◽  
Cell Sorting ◽  
Lymphoblastic Leukemia ◽  
Mononuclear Phagocytes ◽  
Leukemic Cells ◽  
Leukemia Cells ◽  
Normal Bone Marrow ◽  
Normal Bone

Abstract Monoclonal antibodies (MoAbs) have been prepared recently that recognize the three cell-surface receptors for the Fc portion of immunoglobulin (Ig), termed Fc gamma RI (MoAb 32.2), Fc gamma R II (MoAb IV-3), and Fc gamma R III (MoAb 3G8) that are expressed on selected subsets of non-T lymphocyte peripheral blood leukocytes. In the blood, Fc gamma R I is expressed exclusively on monocytes and macrophages, Fc gamma R II on granulocytes, mononuclear phagocytes, platelets, and B cells, and Fc gamma R III on granulocytes and natural killer (NK) cells. We have examined the expression of these molecules on normal bone marrow (BM) cells and on leukemia cells from the blood and/or BM in order to determine their normal ontogeny as well as their distribution on leukemic cells. BM was obtained from six normal volunteers and from 170 patients with newly diagnosed acute leukemia. Normal BM cells were found to express Fc gamma R I, II, and III with the following percentages: 40%, 58%, and 56%, respectively. Cell sorting revealed that both Fc gamma R I and Fc gamma R II were detectable on all subclasses of myeloid precursors as early as myeloblasts. Cell sorting experiments revealed that 66% of the granulocyte-monocyte colony-forming cells (CFU-GM) and 50% of erythroid burst-forming units (BFU-E) were Fc gamma R II positive with only 20% and 28%, respectively, of CFU-GM and BFU-E were Fc gamma R I positive. Acute myeloid leukemia (AML) cells expressed the three receptors with the following frequency (n = 146): Fc gamma R I, 58%; Fc gamma R II, 67%; and Fc gamma R III, 26% of patients. Despite the fact that Fc gamma R I is only expressed on monocytes among blood cells, AML cells without monocytoid differentiation (French-American-British [FAB]M1, M2, M3, M6) were sometimes positive for this receptor. However, Fc gamma R I was highly correlated with FAB M4 and M5 morphology (P less than .001). Fc gamma R II was also correlated with FAB M4 and M5 morphology (P = .003). Cells from 11 patients with acute lymphoblastic leukemia were negative for Fc gamma R I, but six cases were positive for Fc gamma R II and III (not the same patients). These studies demonstrate that Ig Fc gamma R are acquired during normal differentiation in the BM at or before the level of colony-forming units. In addition, we show that acute leukemia cells commonly express Fc gamma R.

scholarly journals CD7+ and CD56+ Myeloid/Natural Killer Cell Precursor Acute Leukemia: A Distinct Hematolymphoid Disease Entity

Blood ◽  
1997 ◽  
Vol 90 (6) ◽  
pp. 2417-2428 ◽  
Author(s):  
Ritsuro Suzuki ◽  
Kazuhito Yamamoto ◽  
Masao Seto ◽  
Yoshitoyo Kagami ◽  
Michinori Ogura ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Acute Leukemia ◽  
Natural Killer ◽  
Nk Cell ◽  
Bone Marrow Involvement ◽  
Leukemic Cells ◽  
Allogeneic Bone ◽  
Disease Entity ◽  
Cell Precursor

Abstract The disease spectrum of natural killer (NK) cell leukemias and lymphomas has recently been expanding with the continuing evolution in diagnostic concepts. We describe here seven cases of acute leukemia of conceivable myeloid and NK cell precursor phenotype in six men and one woman varying from 19 to 59 years of age (median, 46 years). Striking extramedullary involvement was evident at initial presentation, with peripheral lymphadenopathy and/or mediastinal masses. Two lacked any leukemic cells in the bone marrow at diagnosis. Using cytochemical myeloperoxidase staining, less than 3% of the leukemic cells showed positive reactivity. However, expression of CD7, CD33, CD34, CD56, and frequently HLA-DR, but not other NK, T-cell, and B-cell markers was observed. Cytoplasmic CD3 was detected in three of the cases by flow cytometry and in six by Northern blotting, suggesting an origin from common progenitors between the NK cell and myeloid lineages. All but one presented germline configurations of the T-cell receptor β and γ chain genes and Ig heavy chain gene. With regard to morphology, the cells were generally L2-shaped, with variation in cell size, round to moderately irregular nuclei and prominent nucleoli, pale cytoplasm, and a lack of azurophilic granules. Histopathologic examination of biopsied specimens of extramedullary tumors showed a lymphoblast-like morphology, implying the differential diagnostic problem from lymphoblastic lymphomas, especially in cases lacking bone marrow involvement. Three patients were successfully treated with chemotherapy for acute myeloid leukemia (AML), whereas three other patients proved refractory to chemotherapeutic regimens for lymphoid malignancies, although two responded to subsequent AML chemotherapy. However, despite intensive chemotherapy, including allogeneic bone marrow transplantation, most persued fatal courses within 41 months. These data suggested that the CD7+ and CD56+ myeloid/NK cell precursor acute leukemia might constitute a distinct biologic and clinical disease entity. Its recognition appears to be particularly important for the clinicopathologic evaluation of CD56+ hematolymphoid malignancies and the development of therapeutic approaches to such disease.

Characteristics of De Novo Acute Leukemia Patients with Glycosylphosphatidylinositol (GPI) Protein-Negative Population of Leukemic Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4462-4462
Author(s):  
Hideyoshi Noji ◽  
Tsutomu Shichishima ◽  
Masatoshi Okamoto ◽  
Kazuhiko Ikeda ◽  
Akiko Nakamura ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Leukemia ◽  
De Novo ◽  
Bone Marrow Failure ◽  
Flow Cytometric Analysis ◽  
Leukemic Cells ◽  
Remission Induction ◽  
Color Flow ◽  
Flow Cytometric ◽  
Number Of Patients

Abstract Paroxysmal nocturnal hemoglobinuria (PNH) is considered to be an acquired stem cell disorder affecting all hematopoietic lineages, which lack GPI-anchored membrane proteins, such as CD59, because of abnormalities in the phosphatidylinositol glycan-class A (PIG-A) gene. Also, PNH is one disorder of bone marrow failure syndromes, including aplastic anemia and myelodysplastic syndrome, which are considered as pre-leukemic states. In this study, to know some characteristics of patients with de novo acute leukemia, we investigated expression of CD59 in leukemic cells from 25 patients (female: male=8: 17; mean age ± standard deviation, 57.8 ± 19.5 years) with de novo acute leukemia by single-color flow cytometric analysis. In addition, the PIG-A gene from CD59− leukemic cells sorted by FACS Vantage in 3 patients with acute leukemia was examined by sequence analysis. All the patients had no past history of PNH. Based on the French-American-British criteria, the diagnosis and subtypes of acute leukemia were determined. The number of patients with subtypes M1, M2, M3, M4, M5, and M7 was 1, 14, 2, 4, 2, and 2, respectively. Two of the patients were classified into acute myeloid leukemia with trilineage myelodysplasia from morphological findings in bone marrow. Chromosomal analyses presented abnormal karyotypes in 14 of 25 patients. Flow cytometric analyses showed that leukemic cells from 16 of 25 patients (64%) had negative populations of CD59 expression and the proportion of the populations was 63.3 ± 25.7%, suggesting the possibility that CD59− leukemic cells from patients with de novo acute leukemia might be derived from PNH clones. In fact, the PIG-A gene analyses showed that monoclonal or oligoclonal PIG-A mutations in coding region were found in leukemic cells from 3 patients with CD59− leukemic cells and all of the clones with the PIG-A mutations were minor. Then, various clinical parameters, including rate of complete remission for remission-induction chemotherapy, peripheral blood, bone marrow blood, and laboratory findings, and results of chromosomal analyses were statistically compared between 2 groups of patients with (n=16) and without (n=9) CD59− leukemic cells. The reticulocyte counts (10.5 ± 13.0 x 104/μl) and proportions of bone marrow erythroblasts (17.5 ± 13.9%) in patients with only CD59+ leukemic cells were significantly higher than those (2.5 ± 1.7 x 104/μl, p&lt;0.05; and 5.6 ± 6.2%, p&lt;0.01, respectively) in patients with CD59− leukemic cells. The proportions of bone marrow blasts (69.3 ± 21.1%) in patients with CD59− leukemic cells were significantly higher than those (45.5 ± 19.3%, p&lt;0.02) in patients with only CD59+ leukemic cells. In conclusion, our findings indicate that leukemic cells derived from PNH clones may be common in de novo acute leukemia patients, suggesting that bone marrow failure may have already occurred in localized bone marrow even in de novo acute leukemia.

Modification of Gene Expression in Mesenchymal Stromal Cells of the Leukemia Patients during Chemotherapy

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5065-5065
Author(s):  
Tamara Sorokina ◽  
Irina Shipounova ◽  
Alexey Bigildeev ◽  
Nina I. Drize ◽  
Larisa A. Kuzmina ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Acute Leukemia ◽  
Fetal Calf Serum ◽  
Calf Serum ◽  
Leukemic Cell ◽  
Expression Level ◽  
Leukemic Cells ◽  
Disease Manifestation ◽  
Relative Expression Level

Abstract Background In patients with acute leukemia the stromal microenvironment is deeply modified. Disturbances in signaling pathways, genetic abnormalities and functional changes in mesenchymal cells of these patients have been previously described. Chemotherapy also affect stromal progenitor cells. A damaged microenvironment might impair hematopoiesis in acute leukemia patients. Aims To investigate the relative expression level in MMSCs and CFU-Fs, derived from the bone marrow (BM) of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) patients before and over the course of chemotherapy. Methods 54 newly diagnosed cases (33 AML, 21 ALL) were involved in the study after informed consent. BM was aspirated prior to any treatment (time-point 0) and at days 37, 100 and 180 since the beginning of treatment of acute leukemia. MMSCs were cultured in aMEM with 10% fetal calf serum, CFU-Fs, in aMEM with 20% fetal calf serum. The relative expression level (REL) of different genes was measured by TaqMan RQ-PCR. As a control MMSCs and CFU-Fs from 88 healthy donors were used. Results At the time of the disease manifestation the analysis of gene expression in MMSCs from acute leukemia patients revealed a significant increase in the REL of genes which regulate immune system responses and thereby can influence on the leukemic cell proliferation and migration (IL-6, IL-8, IL-1b and IL-1R1) (Pic.1). Also at the time of the diagnosis an increase in REL of genes, that are responsible for hematopoiesis regulation, was observed. For example, the REL of CSF1 that can influence on leukemic cells proliferation was increased at the disease manifestation and became normal during the treatment. The same dynamics was observed in the REL of JAG1 that has an antiapoptotic effect on leukemic cells. The REL of LIF had been also significantly increased at the disease manifestation, reflecting the efforts of MMSCs to inhibit leukemic proliferation. Chemotherapy affected REL of the studied genes differently. The treatment lead to the downregulation of IGF, TGFB1 and TGFB2 (Pic.2). As far asTGFB1 and 2 inhibit the differentiation of mesenchymal stem cells, and IGF is associated with myelodysplastic changes in elderly bone marrow, so their downregulation may refer to the effectiveness of therapy. The REL of genes regulating MMSC proliferation (PDGFRa and PDGFRb, FGF2, FGFR1 and 2) increased during chemotherapy. Exploring cell adhesion molecules, the decrease in the REL of their encoding genes was observed. As far as VCAM facilitate the leukemic cell extravasation and ICAM was shown to depress the Th17 cell differentiation, the down-regulation of their genes may reflect the microenvironment restoration. The influence of chemotherapy lead to decrease in REL of genes, associated with MMSCs differentiation (BGLAP and SOX9 (Pic.3)), reflecting the mechanism of the blocking of MMSCs migration and differentiation under the stress conditions. The alterations of bone marrow stroma were more pronounced in patients who didn't achieve remission. The REL of 9 genes was studied in CFU-F colonies. There were no differences in gene expression in CFU-Fs before the treatment, except for an increase in the REL of PPARg in acute leukemia CFU-Fs. During the treatment, a decrease in the REL of SPP1 and an increase in the REL of FGFR1 and 2 were observed. Conclusion Therefore, chemotherapy used does not impair the functional ability of MMSCs and CFU-Fs, but influence on their gene expression profile. The two types of precursors are affected differently, indicating their different differentiation level and functions. Figure 1 Figure 1. Figure 2 Figure 2. Figure 3 Figure 3. Disclosures No relevant conflicts of interest to declare.

scholarly journals CD7+ and CD56+ Myeloid/Natural Killer Cell Precursor Acute Leukemia: A Distinct Hematolymphoid Disease Entity

Blood ◽  
1997 ◽  
Vol 90 (6) ◽  
pp. 2417-2428 ◽  
Author(s):  
Ritsuro Suzuki ◽  
Kazuhito Yamamoto ◽  
Masao Seto ◽  
Yoshitoyo Kagami ◽  
Michinori Ogura ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Acute Leukemia ◽  
Natural Killer ◽  
Nk Cell ◽  
Bone Marrow Involvement ◽  
Leukemic Cells ◽  
Allogeneic Bone ◽  
Disease Entity ◽  
Cell Precursor

The disease spectrum of natural killer (NK) cell leukemias and lymphomas has recently been expanding with the continuing evolution in diagnostic concepts. We describe here seven cases of acute leukemia of conceivable myeloid and NK cell precursor phenotype in six men and one woman varying from 19 to 59 years of age (median, 46 years). Striking extramedullary involvement was evident at initial presentation, with peripheral lymphadenopathy and/or mediastinal masses. Two lacked any leukemic cells in the bone marrow at diagnosis. Using cytochemical myeloperoxidase staining, less than 3% of the leukemic cells showed positive reactivity. However, expression of CD7, CD33, CD34, CD56, and frequently HLA-DR, but not other NK, T-cell, and B-cell markers was observed. Cytoplasmic CD3 was detected in three of the cases by flow cytometry and in six by Northern blotting, suggesting an origin from common progenitors between the NK cell and myeloid lineages. All but one presented germline configurations of the T-cell receptor β and γ chain genes and Ig heavy chain gene. With regard to morphology, the cells were generally L2-shaped, with variation in cell size, round to moderately irregular nuclei and prominent nucleoli, pale cytoplasm, and a lack of azurophilic granules. Histopathologic examination of biopsied specimens of extramedullary tumors showed a lymphoblast-like morphology, implying the differential diagnostic problem from lymphoblastic lymphomas, especially in cases lacking bone marrow involvement. Three patients were successfully treated with chemotherapy for acute myeloid leukemia (AML), whereas three other patients proved refractory to chemotherapeutic regimens for lymphoid malignancies, although two responded to subsequent AML chemotherapy. However, despite intensive chemotherapy, including allogeneic bone marrow transplantation, most persued fatal courses within 41 months. These data suggested that the CD7+ and CD56+ myeloid/NK cell precursor acute leukemia might constitute a distinct biologic and clinical disease entity. Its recognition appears to be particularly important for the clinicopathologic evaluation of CD56+ hematolymphoid malignancies and the development of therapeutic approaches to such disease.

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