Dasatinib Promotes the Maturation of Healthy Donors and Chronic Myelogenous Leukemia Patients Derived Dendritic Cells

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 53-54
Author(s):  
Wangjun Cao ◽  
Lin He ◽  
Hong Zheng ◽  
Xiaobing Huang ◽  
Xi Yang ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Chronic Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Control Group ◽  
Surface Markers ◽  
Expression Levels ◽  
Hla Dr ◽  
Healthy Donors ◽  
Significant Difference ◽  
Enhanced Expression

Dasatinib has been discovered to obtain immunomodulatory effects in addition to the targeting effect towards BCR-ABL in chronic myelogenous leukemia (CML) patients. But the effect of dasatinib on dendritic cells (DCs) is still not fully understood. Objective To investigate the effect of dasatinib on the maturation of monocyte derived dendritic cells (moDCs) from healthy donors (HDs) and CML patients. Method Peripheral blood mononuclear cells (PBMCs) were isolated from HDs (n=14) and CML patients (n=14) who had got remission of MR4.5 with imatinib treatment. The generation of moDCs was completed after 7 days of incubation in DC I medium, and another 3 days of incubation in DC II medium with or without 25nM dasatinib. On the 10th day, the moDCs were harvested and analyzed for the expression of surface markers CD83, CD80, CD86, CD40 and HLA-DR to reflect the maturation of the moDCs by flow cytometry. Results When analyzing the moDCs from all the 14 HDs together, dasatinib significantly enhanced the expression levels of the surface marker CD83 (P=0.039), CD40 (P=0.002) and HLA-DR (P=0.000) on moDCs compared with the control group, but there was no statistically significant difference in CD80 (P=0.073) and CD86 (P=0.897). Differently, when analyzing the moDCs derived from all the 14 patients together, there was no statistically significant difference in the expression levels of CD80 (P=0.086), CD86 (P=0.166), CD83 (P=0.674), CD40 (P=0.574) and HLA-DR (P=0.561) on moDCs between the dasatinib group and the control group. However, moDCs derived from 3 of the 14 patients show the enhanced expression of all the five surface makers with dasatinib administration compared to the control group. Besides, the moDCs derived from 6 of the 14 patients show the enhanced expression of at least one of the five surface markers. Notably, compared with moDCs derived from HD group (n=14), moDCs from patient group (n=14) express lower levels of CD80 (P=0.340), CD86 (P=0.007), CD40 (P=0.010), CD83 (P=0.019) and HLA-DR (P=0.036). Conclusion Dasatinib at the concentration of 25nM can efficiently promote the maturation of HD-derived moDCs in vitro, whereas this effect only occurs in part of the CML patients. And the moDCs from patients generally show much lower levels of the maturation associated surface makers compared with moDCs from HDs. Dasatinib shows potential as a DC adjuvant to be applied in DC-based therapeutic strategies, such as DC vaccine and DC cell-therapy. Disclosures No relevant conflicts of interest to declare.

scholarly journals Pomalidomide Promotes the Maturation of Healthy Donors and Multiple Myeloma Patients Derived-Dendritic Cells

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4702-4702
Author(s):  
Xi Wang ◽  
Feifei Che ◽  
Wanjun Cao ◽  
Zichen Ye ◽  
Hong Zheng ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Dendritic Cells ◽  
Peripheral Blood ◽  
Conflicts Of Interest ◽  
Control Group ◽  
Incubation System ◽  
Hla Dr ◽  
Healthy Donors ◽  
Tnf Α ◽  
Significant Difference

Abstract Abstract: Objective To investigate the effect of pomalidomide on the maturation of monocyte derived dendritic cells (moDCs) from healthy donors (HDs) and multiple myeloma (MM) patients. Method Peripheral blood mononuclear cells (PBMCs) were isolated from the peripheral blood of HDs and MM patients. The generation of moDCs from monocytes in PBMCs was conducted by the incubation of 7 days in a medium consisting of RPMI 1640 medium, 5% human serum, 800U/mL GM-CSF, 500U/mL IL-4, 100U/mL penicillin and 0.1mg/mL streptomycin. During this period, the incubation system was administrated with pomalidomide at 10 µM or 1×PBS as the control group. On the 8 th day, cells were harvested, and the immunophenotyping of cells were analyzed by the flow cytometry. The CD80+CD86+ cell population in total cells is gated as DCs in the FACS analyzing system. Then, the median fluorescence intensity (MFI) of surface markers CD40 and HLA-DR as well as the proportion of CD40+ DCs and HLA-DR+ DCs in total DCs were analyzed respectively. In addition, supernatant from the incubation system with or without pomalidomide administration was collected and detected for the concentration of cytokines IL-12, TNF-α and MIP-1α. Results The proportion of CD80+CD86+ cells in total cells was higher in HD group (n=15) than in MM patient group (n=11), but there was no statistically significant difference (93.49%±6.43% vs 77.04%±27.17%, P=0.094). When analyzing all the HD-derived moDCs (n=15), pomalidomide significantly enhanced the MFI of CD40 (P=0.003) and HLA-DR (P=0.040) on moDCs when compared with the control group. Meanwhile, the proportion of CD40+ DCs (P=0.008) and HLA-DR+ DCs (P=0.032) in total DCs was significantly higher in pomalidomide group than in control group. When analyzing all MM patients-derived moDCs (n=11), pomalidomide significantly enhanced the MFI of CD40 (P=0.047) and HLA-DR (P=0.006) on moDCs when compared with the control group. Meanwhile, the proportion of HLA-DR+ DCs in total DCs was significantly higher in pomalidomide group than in the control group (P=0.000). Moreover, pomalidomide treated HD-derived moDCs (n=8) produced 192% IL-12 (P=0.020), 110% TNF-α (P=0.006) and 112% MIP-1α (P=0.055) of untreated moDCs. However, when analyzing MM patients-derived moDCs (n=10), the expression of IL-12 (P=0.458), TNF-α (P=0.377) and MIP-1α (P=0.248) from moDCs showed no significant difference between pomalidomide group and the control group. Conclusions Pomalidomide at 10 µM can promote the maturation of both HD-derived moDCs and MM patients-derived moDCs. Pomalidomide shows potential to be a DC adjuvant for DC-based therapeutic strategies, such as DC vaccine and DC cell-therapy in MM. Key words: Pomalidomide; Monocyte derived Dendritic Cells; Multiple Myeloma; DC Adjuvant Disclosures No relevant conflicts of interest to declare.

Cytokine expression profiles of patients with acute myelogenous leukemia (AML) and non-Hodgkin lymphoma (NHL) detected by multiplex assay

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18530-18530
Author(s):  
V. B. Reddy ◽  
D. K. Oelschlager ◽  
J. S. Nolan ◽  
K. L. Taylor ◽  
J. Post ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Recovery Phase ◽  
Cytokine Expression ◽  
Multiplex Assay ◽  
Myelogenous Leukemia ◽  
Control Group ◽  
Serum Samples ◽  
Expression Levels ◽  
Significant Difference ◽  
Low Levels

18530 Background: To determine the cytokine expression profiles of patients with AML and NHL using a sensitive bead-based Luminex multiplex assay in a routine clinical diagnostic setting. Methods: Blood (plasma/serum) samples were collected from ten AML and five NHL patients. Six control samples from patients diagnosed as non-neoplastic/non-autoimmune/non-inflammatory were also analyzed for comparison. All samples were frozen prior to analysis. Using a bead-based Luminex assay (Human Cytokine 8-Plex Assay, Bio- Rad, Hercules, CA) we analyzed these samples for a panel of cytokines (IL-2, IL-4, IL-6, IL-10, GM-CSF, IFN-gamma, and TNF-alpha). This assay uses polystyrene microspheres, which provides simultaneous quantitation of these cytokines in a single sample. The expression levels were presented in picograms/mL. Average values for each of these markers were obtained for each group of patients (AML versus NHL versus Controls), and their expression levels were compared using χ2 analysis. Results: Overall, there was a significant difference in the expression profiles of all these cytokines among three patients groups (χ2, P < 0.001). All cytokines were consistently expressed at low levels in NHL patients as compared to control group. However, the levels of IL-6 and IL-8 were increased by 2.7 and 5.8 times, respectively in AML patients as compared to controls. Conclusions: The low levels of cytokines in NHL and AML patients suggest suppressed immune system in these two disease conditions; however, these findings warrant further studies to explore the underlying mechanisms for the increased levels of IL-6 and IL-8 in AML patients. Currently, studies are in progress to compare the levels of cytokines measured by Luminiex assay in different stages of leukemias and lymphomas (initial, post treatment and recovery phase etc.). These studies are partially funded by grants from the National Institute of Health/National Cancer Institute (RO1-CA98932–01 and U24-CA086359). No significant financial relationships to disclose.

scholarly journals TET1 Knockdown Inhibits Porphyromonas gingivalis LPS/IFN-γ-Induced M1 Macrophage Polarization through the NF-κB Pathway in THP-1 Cells

2019 ◽  
Vol 20 (8) ◽  
pp. 2023 ◽  
Author(s):  
Huang ◽  
Tian ◽  
Li ◽  
Xu
Keyword(s):  
Porphyromonas Gingivalis ◽  
Periodontal Diseases ◽  
Macrophage Polarization ◽  
Control Group ◽  
M1 Macrophages ◽  
Expression Levels ◽  
Hla Dr ◽  
M1 Macrophage ◽  
Significant Difference ◽  
Ifn Γ

Tet-eleven translocation 1 (TET1) is a dioxygenase that plays an important role in decreasing the abundance of DNA methylation and changing the expression levels of specific genes related to inflammation. Porphyromonas gingivalis (Pg.) lipopolysaccharide (LPS) can induce periodontal diseases that present with severe bone loss and collagen fiber destruction accompanied by a high number of M1 macrophages. M1-polarized macrophages are pivotal immune cells that promote the progression of the periodontal inflammatory response, but the function of TET1 during M1 macrophage activation is still unknown. Our results showed that the mRNA and protein expression levels of TET1 decreased in THP-1 cells during M1 macrophage differentiation. TET1 knockdown resulted in a significant decrease in the production of proinflammatory markers such as IL-6, TNF-α, CCL2, and HLA-DR in Pg. LPS/IFN-γ- and Escherichia coli (E. coli) LPS/IFN-γ-induced M1 macrophages. Mechanistically, TET1 knockdown downregulated the activity of the NF-κB signaling pathway. After treatment with the NF-κB inhibitor BAY 11-7082, M1 marker expression showed no significant difference between the TET1 knockdown group and the control group. Taken together, these results suggest that TET1 depletion inhibited Pg. LPS/IFN-γ-induced M1 macrophage polarization through the NF-κB pathway in THP-1 cells.

Depletion of Circulating Plasmacytoid Dendritic Cells in Chronic Myelogenous Leukemia and Their Restoration after Interferon-alpha or Imatinib Mesylate.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2204-2204
Author(s):  
Alexis Rossignol ◽  
Anne Barra ◽  
Lydia Roy ◽  
Francois Guilhot ◽  
Ali G. Turhan ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Imatinib Mesylate ◽  
Chronic Myelogenous Leukemia ◽  
Critical Role ◽  
Plasmacytoid Dendritic Cells ◽  
Myelogenous Leukemia ◽  
Cell Populations ◽  
Healthy Donors ◽  
Cytogenetic Remission

Abstract It is currently established that the immune system plays a critical role in the control of chronic myelogenous leukemia (CML). Several cell populations including T cells, dendritic cells (DC) and NK cells have been shown to exhibit potential anti-leukemic activities. The possible role of plasmacytoid dendritic cells (pDC) in this anti-leukemic response has not been explored so far. As pDC are the major source of interferon(IFN)-α in vivo, the frequency and the function of circulating pDC were compared in CML patients and in healthy subjects. Three groups of CML patients were studied: chronic phase patients (CP) (i.e. at diagnosis or unresponsive to treatment); patients in complete/major cytogenetic remission induced by IFN-α and patients in complete/major cytogenetic remission induced by imatinib mesylate (IM). Flow cytometric analysis of pDC (assessed by the strong co-expression of CD123 and CD303, formerly BDCA2) showed a dramatic depletion of pDC compartment in CP patients (n = 11) as compared to healthy donors (n = 9) (0.99 versus 5.71 pDC/μL of blood, respectively). Moreover, their functional capacity to produce IFN-α after peripheral blood mononuclear cells (PBMC) stimulation with influenza virus was abolished (883 versus 8201 pg/ml of supernatant, respectively). Patients treated with IFN-α exhibited a complete and long-termed restoration of pDC compartment (4.88 pDC/μL of blood) and of IFN-α production (6932 pg/ml), which was sustained even after the treatment was stopped. In contrast, although IM therapy led to the complete restoration of IFN-α production (6662 pg/ml), its effect on circulating pDC number remained solely partial (2.82 pDC/μL of blood). This last observation and the absence of any linear relationship between pDC number and IFN-α production in patients in complete remission suggested that treatments, and more particularly IM, were able to induce “pDC-independent” pathways of in vivo IFN-α production. Consistently with this hypothesis, we found that pDC-depleted PBMC from patients in cytogenetic remission were able to produce IFN-α, whereas those from healthy donors were not. As a conclusion, our results show for the first time that IFN-α and IM treatments reverse the quantitative and functional impairment of pDC compartment in CP CML patients. They also suggest that these treatments are able to induce differentiation mechanisms leading to the generation of new IFN-α producing cell populations.

scholarly journals Murine hepatoma treatment with mature dendritic cells stimulated by Trichinella spiralis excretory/secretory products

Parasite ◽  
2020 ◽  
Vol 27 ◽  
pp. 47
Author(s):  
Jing Ding ◽  
Xiaolei Liu ◽  
Bin Tang ◽  
Xue Bai ◽  
Yang Wang ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Tumor Growth ◽  
Antitumor Effect ◽  
Trichinella Spiralis ◽  
Critical Role ◽  
Tumor Model ◽  
Control Group ◽  
Tumor Inhibition ◽  
Significant Difference ◽  
Secretory Products

Excretory/Secretory Products (ESPs) of the nematode Trichinella spiralis contain antitumor-active substances that inhibit tumor growth. Mature dendritic cells (DCs) play a critical role in the antitumor immunity of the organism. As pathogen-derived products, it ought to be discussed whether T. spiralis ESPs will reduce the antitumor effect of mature DCs from the host before it is applied to patients’ tumors. Therefore, the aim of this work was to evaluate the immunological effect of DCs stimulated by T. spiralis ESPs in H22 tumor-bearing mice. H22 tumor model mice in this study were randomly divided into four groups according to the treatment: PBS control group, ESP group, DCs group, and DCs stimulated with T. spiralis ESP (ESP+DCs group). The antitumor effect was evaluated by tumor inhibition rate and cytokine detection using ELISA. The results showed significant inhibition in tumor growth in the ESP+DCs, DCs and ESP groups when compared with the PBS control group (p < 0.01, p < 0.01, and p < 0.05, respectively). However, no significant difference was observed on tumor inhibition rates between the ESP+DCs and DCs groups. The decrease in IL-4, IL-6, and IL-10, and the increase in IFN-γ between the DCs and ESP+DCs groups were also not significant. Therefore, DCs stimulated by ESP did not reduce the antitumor effect of mature DCs, which demonstrated that the T. spiralis ESP would not affect the antitumor effect of mature DCs by modulating the immune response of the host, and that ESPs are safe in antitumor immunology when applied in a tumor model mice.

Immunophenotypic Study of Basophils by Multiparameter Flow Cytometry

2008 ◽  
Vol 132 (5) ◽  
pp. 813-819
Author(s):  
Xiaohong Han ◽  
Jeffrey L. Jorgensen ◽  
Archana Brahmandam ◽  
Ellen Schlette ◽  
Yang O. Huh ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Chronic Myelogenous Leukemia ◽  
Peripheral Blood ◽  
Myelogenous Leukemia ◽  
Multiparameter Flow Cytometry ◽  
Color Flow ◽  
Aberrant Expression ◽  
Flow Cytometric ◽  
Hla Dr

Abstract Context.—The immunophenotypic profile of basophils is not yet fully established, and the immunophenotypic changes in chronic myelogenous leukemia are not fully characterized. Objective.—To establish a comprehensive immunophenotypic spectrum of normal basophils and to assess the range of immunophenotypic aberrations of basophils in chronic myelogenous leukemia. Design.—Using 4-color flow cytometry, we compared the immunophenotypic profile of basophils in peripheral blood or bone marrow samples from 20 patients with no evidence of neoplasia to basophils from 15 patients with chronic myelogenous leukemia. Results.—Basophils in control cases were all positive for CD9, CD13, CD22, CD25 (dim), CD33, CD36, CD38 (bright), CD45 (dimmer than lymphocytes and brighter than myeloblasts), and CD123 (bright), and were negative for CD19, CD34, CD64, CD117, and HLA-DR. Basophils in all chronic myelogenous leukemia patients possessed 1 to 5 immunophenotypic aberrancies. The most common aberrancies were underexpression of CD38, followed by aberrant expression of CD64 and underexpression of CD123. CD34 and CD117 were present in cases with basophilic precursors. Myeloblasts showed a distinct immunophenotypic profile, as they typically expressed CD34 and CD117, showed dimmer expression (compared with basophils) of CD38, CD45, and CD123, and lacked expression of CD22. Conclusions.—Flow cytometric immunophenotyping can identify immunophenotypic aberrations of basophils in chronic myelogenous leukemia, and discriminate basophils from myeloblasts.

Imatinib mesylate (STI571) therapy for Philadelphia chromosome–positive chronic myelogenous leukemia in blast phase

Blood ◽  
2002 ◽  
Vol 99 (10) ◽  
pp. 3547-3553 ◽  
Author(s):  
Hagop M. Kantarjian ◽  
Jorge Cortes ◽  
Susan O'Brien ◽  
Francis J. Giles ◽  
Maher Albitar ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Chronic Myelogenous Leukemia ◽  
Response Rate ◽  
Philadelphia Chromosome ◽  
Response To Therapy ◽  
Myelogenous Leukemia ◽  
Control Group ◽  
Blast Phase ◽  
Molecular Abnormalities ◽  
Philadelphia Chromosome Positive

Molecular abnormalities caused by the hybrid Bcr-Abl gene are causally associated with the development and progression of Philadelphia chromosome–positive (Ph+) chronic myelogenous leukemia (CML). Imatinib mesylate (STI571), a specific Bcr-Abl tyrosine-kinase signal-transduction inhibitor, has shown encouraging activity in phase I and II studies of CML. Here, we describe the use of imatinib mesylate to treat 75 patients in blast-phase CML (median age, 53 years; 65 with nonlymphoid and 10 with lymphoid blasts), and compare the results with those of a historical control group treated with standard cytarabine-based therapy. Imatinib mesylate was given as oral doses at 300 to 1000 mg per day and was the first salvage therapy for 47 patients. The objective response rate was 52% (39 of 75 patients: 16 had complete and 3 had partial hematologic response; 12 had hematologic improvement; 7 returned to second chronic phase; and 1 had a complete response in extramedullary blastic disease). Response rates were not different between nonlymphoid and lymphoid groups. The cytogenetic response rate was 16% (12 patients: 5 complete, 3 partial [Ph+ below 35%], and 4 minor [Ph+, 34% to 90%]). The estimated median overall survival was 6.5 months; the estimated 1-year survival was 22%. Response to therapy (landmark analysis at 8 weeks) was associated with survival prolongation. Compared with standard cytarabine combinations, imatinib mesylate therapy was less toxic and produced a higher response rate (55% versus 29%, P = .001), longer median survival (7 versus 4 months, P = .04), and lower 4-week induction mortality (4% versus 15%, P = .07). Imatinib mesylate is currently being tested in combination with other drugs to improve the prognosis for blast-phase CML.

scholarly journals Expression of AIM2 in rheumatoid arthritis and its role on fibroblast-like synoviocyte

2020 ◽  
Author(s):  
fujuan qiu ◽  
Chen Yong ◽  
Qiu Fujuan ◽  
Zhao Xiaofeng ◽  
Xiao Changhong
Keyword(s):  
Rheumatoid Arthritis ◽  
Mtt Assay ◽  
Control Group ◽  
Expression Levels ◽  
Potential Target ◽  
Caspase 1 ◽  
Significant Difference ◽  
And Migration ◽  
Fibroblast Like Synoviocytes ◽  
Proliferation And Migration

Abstract Background To determine whether any differences of AIM2 inflammasome expression levels between rheumatoid arthritis (RA) and osteoarthritis (OA) and investigate the effects of AIM2 when transferred into RA fibroblast-like synoviocytes (RA-FLS).Methods Serum AIM2 levels between OA and RA patients were compared by ELISA. Different expression levels of AIM2, ASC, Caspase-1 and IL-1β between RA and OA synovium were semi-quantified by RT-qPCR and immunohistochemical (IHC) staining. IHC staining were recorded by H scores, and determine the correlation with ESR and CRP levels of RA patients. SiRNA AIM2 was transferred to RA-FLS and observe its effects on proliferation and migration by MTT assay and transwell test respectively.Results In RA sera, no significant difference was observed between OA and RA patients. However, in affected knee synovium, AIM2, ASC, Caspase-1 and IL-1β were expressed higher in RA than that of OA. Plus, H score of AIM2, ASC, and IL-1β were positively correlated to ESR and CRP levels in RA patients. After transferred AIM2 siRNA to FLS and incubation for 48 hours, the proliferation of FLS were significantly inhibited, and the apoptosis rate were significantly increased compared to FLS in control group. However, no effect on migration was detected.Conclusions AIM2 participated in the proliferation of FLS, and might be a potential target for therapy.

scholarly journals The effect of human amniotic epithelial cell on dendritic cell differentiation of peripheral blood monocytes: An experimental study

2020 ◽  
Author(s):  
Bahare Keshavarzi ◽  
Meraj Tabatabaei ◽  
Amir Hasan Zarnani ◽  
Fahime Ramezani Tehrani ◽  
Mahmood Bozorgmehr ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Amniotic Membrane ◽  
Peripheral Blood ◽  
Normal Pregnancy ◽  
Interleukin 4 ◽  
Control Group ◽  
Blood Monocytes ◽  
Peripheral Blood Monocytes ◽  
Dendritic Cell Differentiation ◽  
Significant Difference

Background: The amniotic membrane plays an important role in maintaining a healthy pregnancy. The main population cells from amniotic membrane include human amnion epithelial cells (hAECs) which have been shown to possess immunomodulatory properties. Objective: The proximity of hAECs with monocyte leads to the generation of tollerogenic dendritic cells. Materials and Methods: hAECs were obtained from normal pregnancy. Peripheral blood monocytes were isolated by anti-CD14 MACS method. Co-cultures of monocytes and hAECs were established in Transwell chambers supplemented with granulocytemacrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) in the absence and presence of lipopolysaccharide (LPS) to produce immature and mature DCs, respectively. Immunophenotyping of the obtained DCs was done through flow cytometry and the production of cytokines was measured by ELISA. Mixed leukocyte Reaction (MLR) was also performed for the functional assessment of DCs. Results: Immunophenotyping of [hAECs - Immature DC (iDC)] and [hAECs - iDC] + LPS cells revealed that the expression of CD1a, CD80, CD86, CD40, HLA-DR, and CD83 markers showed no significant difference as compared with the control group (iDCs and mDCs alone). In the [hAECs-iDCs] + LPS cells, the percentage of CD14 cells at the ratio of 1:2.5 showed significant differences compared to the control group. The production of IL-10 and IL-12 showed no significant difference in any of the cultures as compared to the control groups. Also, co-cultured DCs did not inhibit proliferation of lymphocyte. Conclusion: Our findings show that factors secreted from cultured hAECs are unable to generate of tollerogenic dendritic cells. To achieve a better understanding of other mechanisms more investigations are needed. Key words: Amniotic membrane, Dendritic cells, Human placenta, Immunomodulation, Monocyte.

BCR Rearrangement–Negative Chronic Myelogenous Leukemia Revisited

2001 ◽  
Vol 19 (11) ◽  
pp. 2915-2926 ◽  
Author(s):  
Razelle Kurzrock ◽  
Carlos E. Bueso-Ramos ◽  
Hagop Kantarjian ◽  
Emil Freireich ◽  
Susan L. Tucker ◽  
...  
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Blast Crisis ◽  
Chronic Phase ◽  
Interferon Alfa ◽  
Myelogenous Leukemia ◽  
Disease Evolution ◽  
Number Of Patients ◽  
Significant Difference ◽  
Atypical Cml ◽  
Peripheral Blood Smears

PURPOSE: To document the characteristics of patients with major breakpoint cluster region (M-bcr) rearrangement–negative chronic myelogenous leukemia (CML). PATIENTS AND METHODS: The hematopathologist, who was blinded to patients’ molecular status, reviewed the referral bone marrows and peripheral-blood smears from 26 patients with Philadelphia (Ph) translocation–negative CML who lacked Bcr rearrangement (and other evidence of a Bcr-Abl anomaly) and 14 patients (controls) with chronic-phase Ph-positive CML. Clinical data was ascertained by chart review. RESULTS: Among the 26 M-bcr rearrangement–negative CML patients, three pathologic subtypes emerged: (1) patients indistinguishable from classic CML (n = 9), (2) patients with atypical CML (n = 8), and (3) patients with chronic neutrophilic leukemia (n = 9). Among the 14 patients with Ph-positive CML who were included in the blinded review, 13 were classified as classic CML, and one was classified as atypical CML. The only statistically significant difference between M-bcr rearrangement–negative subgroups was in the proportion of patients having karyotypic abnormalities, an observation common only in patients with atypical CML (P = 0.008). However, the small number of patients in each subgroup limited our ability to differentiate between them. Interferon alfa induced complete hematologic remission in five of 14 patients; four of these remissions lasted more than 5 years. Only one of 26 patients developed blast crisis. The median survival of the 26 patients was 37 months. CONCLUSION: Patients with M-bcr rearrangement–negative CML fall into three morphologic subgroups. Disease evolution does not generally involve blastic transformation. Instead, patients show progressive organomegaly, leukocytosis, anemia, and thrombocytosis. Some patients in each subgroup can respond to interferon alfa.

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