National Cancer Institute®
Last Modified: June 1, 2002
UI - 11920209
AU - Da Silva N; Meyer-Monard S; Menot ML; Parrado A; Lebel A; Balitrand N;
TI - Fenaux P; Miclea JM; Rousselot P; Degos L; Dombret H; Chomienne C Functional G-CSF pathways in t(8;21) leukemic cells allow for differentiation induction and degradation of AML1-ETO.
SO - Hematol J 2000;1(5):316-28
AD - Laboratoire de Biologie Cellulaire Hematopoietique (LBCH), INSERM E 00-03, et EA 316 Universite Paris 7, Hopital Saint-Louis, 1 Avenue Claude Vellefaux, 75754 Paris Cedex 10, France. firstname.lastname@example.org
INTRODUCTION: Efficacy of differentiating agents requires that their specific cellular targets are still expressed and functional in the leukemic cells. One hypothesis to target sensitive cells is to select leukemic clones which harbor disrupted transcription factors. CBFalpha and CBFbeta are core-binding proteins which have been identified as transcription regulators of hematopoietic genes and shown to be altered in numerous leukemias. In M2 AML, the t(8;21) translocation, CBFalpha (AML1) is altered and produced as the AML1-ETO fusion protein. The fusion protein blocks transcription and differentiation mediated by G-CSF. Interestingly, AML1-ETO leukemic cell lines are sensitive to numerous cytokines in vitro and can be induced to differentiate in the presence of G-CSF and PMA. MATERIALS AND METHODS: As in the APL differentiation model, primary culture provides a useful tool for therapeutic screening of differentiation inducers, we analysed the in vitro sensitivity of 10 fresh M2 AML t(8;21) leukemic samples to G-CSF and the functionality of G-CSF intracellular pathways. In vitro data were compared with in vivo data from four patients treated with rhG-CSF at the dosage of 5 microg/kg/day i.v. for two to three weeks before the initiation of AML induction chemotherapy and immunophenotypic analysis performed weekly to monitor in vivo differentiation. RESULTS: In vitro, an increase in CD34+ cells expressing differentiation antigens (CD11b, CD13 or CD15) was noted along with a decrease of immature CD34+/differentiation antigen negative cells. After two weeks of a daily rhG-CSF administration in vivo, a significant, albeit transient, decrease of blast count was achieved, concomitant with an increase in differentiated leukemic cells suggesting that in vivo differentiation occurs. Fresh t(8;21) leukemic cells possess functional G-CSF signaling pathways as normal activity and kinetics of STAT1 and STAT3 binding was observed. Furthermore, differentiation induction leads to a subsequent degradation of the AML1-ETO oncoprotein. CONCLUSION: The data presented here supports the claim that G-CSF can induce in vitro and in vivo differentiation of M2 AML t(8;21) cells.
UI - 12014211
AU - Lee DG; Choi SM; Choi JH; Yoo JH; Park YH; Kim YJ; Lee S; Min CK; Kim
TI - HJ; Kim DW; Lee JW; Min WS; Shin WS; Kim CC Selective bowel decontamination for the prevention of infection in acute myelogenous leukemia: a prospective randomized trial.
SO - Korean J Intern Med 2002 Mar;17(1):38-44
AD - Department of Internal Medicine, Catholic University College of Medicine, Seoul, Korea.
BACKGROUND: Infection is still a frequent cause of morbidity and mortality in acute myelogenous leukemia (AML) patients receiving chemotherapy. Recently the main cause of infection has changed from gram-negative to gram-positive bacteria and the resistance to antibiotics has increased. This study aimed to access the effectiveness of antimicrobial prophylaxis (AP) with orally absorbable antibiotics. METHODS: Ninety-five AML patients receiving chemotherapy at Catholic 1999 were randomly divided into the AP group (250 mg ciprofloxacin twice a day, 150 mg roxithromycin twice a day, 50 mg fluconazole once a day) and the control group for a prospective analysis. RESULTS: The incidence of fever was 82.6% in the AP group and 91.6% in the control group (p = 0.15). Though classification and sites of infections showed no difference between the two groups, the catheter associated infection occurred more frequently in the AP group in significance. The time interval between initiation of chemotherapy and onset of fever, white blood cell (WBC) count at the onset of fever, duration of leukopenia (WBC < 1,000/mm3), duration of systemic antibiotic therapy, mortality due to infection and hospitalization period from the data starting chemotherapy showed no differences between the two groups. Infections due to gram negative bacteria decreased to 33.3% in the AP group (vs. 92% in the control group), but infections due to gram positive bacteria increased to 66.7% (vs. 8% in the control group). Gram negative bacteria showed 100% resistance to ciprofloxacin in the AP group and gram-positive bacteria showed 90-100% resistance to erythromycin, regardless of the presence of AP. CONCLUSION: The AP could not reduce the occurrence of infection or infection associated death in AML patients receiving chemotherapy. On considering increased gram-positive infection and resistance to fluoroquinolone and macrolide, routine prescription of AP should be reconsidered. Further studies that assess the effectiveness of AP in other malignancies, aplastic anemia and bone marrow transplantation are required.
UI - 10609780
AU - Matsumoto K; Anasetti C
TI - The role of T cell costimulation by CD80 in the initiation and maintenance of the immune response to human leukemia.
SO - Leuk Lymphoma 1999 Nov;35(5-6):427-35
AD - Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Most human myeloid leukemias express both class I and class II HLA and it has been postulated that leukemia-associated peptides are presented by those molecules. It is possible, however, that leukemia cells escape the immune surveillance by lacking expression of "costimulatory" molecules required for activating the immune response. Human erythroleukemia line (HEL) has been the subject of previous detailed studies demonstrating surface expression of bona fide HLA molecules but inability to stimulate allogeneic response of proliferative or cytolytic T cells. We found that an HLA-DR+ subclone (HEL-DR+) expresses LFA-1, LFA-3, ICAM-1, ICAM-3, but neither CD80 nor CD86 on the surface. Transfection of CD80 cDNA into HEL-DR+ cells induced the allogeneic response of purified T cells from both cord blood and peripheral blood of adult donors, demonstrating that CD80 expression could lead to accessory cell-independent activation of naive T cells. Priming allogeneic peripheral blood T cells by HEL-DR+/CD80+ also lead to generation of cytotoxic T lymphocytes that lysed both HEL-DR+/CD80+ and wild type HEL-DR+ equally well, confirming CD80 expression is required only in the CTL induction phase but not in the CTL effector phase. We established and maintained alloproliferative T cell clones from adult blood by stimulation with the HEL-DR+/CD80+ line. The clones could respond not only to HEL-DR+/CD80+ line but also to the HEL-DR+ line; however, the proliferative response to HEL-DR+/CD80+ was amplified and sustained compared to the short-lived response to wild type HEL-DR+ cells. Therefore, expression of CD80 by HEL-DR+ cells was determinant both to initiate and sustain the T cell response. These experiments support the hypothesis that lack of expression of "costimulatory" molecules for T cells contributes to leukemia escape from immune surveillance, and provide preliminary data for the use of CD80 transfection in the immunotherapy of human leukemia.
UI - 11911279
AU - Bruel A; Paschke S; Jainta S; Zhang Y; Vassy J; Rigaut JP; Beil M
TI - Remodeling of vimentin cytoskeleton correlates with enhanced motility of promyelocytic leukemia cells during differentiation induced by retinoic acid.
SO - Anticancer Res 2001 Nov-Dec;21(6A):3973-80
AD - Institute of Hematology, Hospital St. Louis, Paris, France. email@example.com
The intermediate filament (IFs) cytoskeleton is one of the major determinants for the mechanical properties of cytoplasm. Vimentin is the major IFs protein in peripheral blood neutrophils. We investigated its expression and function during neutrophil differentiation using the promyelocytic leukemia cell line NB4. The differentiation of NB4 cells along the neutrophil lineage and the monocytic pathway was induced by all-trans retinoic acid (ATRA) and phorbol esters (PMA), respectively. We demonstrated a down-regulation of vimentin after ATRA treatment of NB4 cells by immunoblotting and immunofluorescence. The architecture of the vimentin cytoskeleton in differentiated NB4 cells resembled that observed in mature neutrophils. In contrast, we showed a slight increase of vimentin content in phorbol ester (PMA)-treated NB4 cells. The structural features of the vimentin cytoskeleton obtained by image analysis showed significant differences in network density and directionality between ATRA-treated NB4 cells and controls. The functional consequence of the cytoskeletal remodeling for the mechanical properties of NB4 cells was assessed in migration assays. After ATRA treatment, we found a 4-fold increased migration of NB4 cells across transwell membranes with a 8 microm pore size without any cell size modification. No significant differences between PMA-treated NB4 cells and control cells could be observed using similar tests. These results indicate that both vimentin expression and network architecture are tightly controlled during neutrophil differentiation to regulate the mechanical properties of these cells.
UI - 12034528
AU - Aventin A; Espadaler M; Casas S; Duarte J; Nomdedeu J; Sierra J
TI - Chromosome 16 inversion-associated translocations in acute myeloid leukemia elucidated using a dual-color CBFB DNA probe.
SO - Cancer Genet Cytogenet 2002 Apr 15;134(2):142-4
AD - Department of Hematology, University Hospital Sant Pau, Barcelona, Spain. firstname.lastname@example.org
We describe two cases of acute myelomonocytic leukemia with eosinophilia (AML-M4Eo) that were diagnosed with an inv(16)(p13q22) based on conventional cytogenetics (CC) and fluorescence in situ hybridization (FISH) technique using a chromosome 16p arm specific paint probe. Additional FISH analysis with a dual-color CBFB DNA probe showed that the 3' portion of the CBFB gene was translocated to chromosome 10p13 in the first patient and 1p36 in the other. These two cases indicate that some inv(16)(p13q22) identified by CC and FISH with chromosome arm-specific painting probe may represent cases of inversion-associated translocation. We suggest that all cases with inv(16)(p13q22) should be investigated by FISH with appropriate probes for a possible translocation of 16q22-->qter to another chromosome.
UI - 11929748
AU - Dong S; Tweardy DJ
TI - Interactions of STAT5b-RARalpha, a novel acute promyelocytic leukemia fusion protein, with retinoic acid receptor and STAT3 signaling pathways.
SO - Blood 2002 Apr 15;99(8):2637-46
AD - Section of Infectious Disease, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Signal transducer and activator of transcription (STAT) 5b-retinoic acid receptor (RAR) alpha is the fifth fusion protein identified in acute promyelocytic leukemia (APL). Initially described in a patient with all-trans retinoic acid (ATRA)-unresponsive disease, STAT5b-RARalpha resulted from an interstitial deletion on chromosome 17. To determine the molecular mechanisms of myeloid leukemogenesis and maturation arrest in STAT5b-RARalpha(+) APL and its unresponsiveness to ATRA, we examined the effect of STAT5b-RARalpha on the activity of myeloid transcription factors including RARalpha/retinoid X receptor (RXR) alpha, STAT3, and STAT5 as well as its molecular interactions with the nuclear receptor corepressor, SMRT, and nuclear receptor coactivator, TRAM-1. STAT5b-RARalpha bound to retinoic acid response elements (RAREs) both as a homodimer and as a heterodimer with RXRalpha and inhibited wild-type RARalpha/RXRalpha transactivation. Although STAT5b-RARalpha had no effect on ligand-induced STAT5b activation, it enhanced interleukin 6-induced STAT3-dependent reporter activity, an effect shared by other APL fusion proteins including promyelocytic leukemia-RARalpha and promyelocytic leukemia zinc finger (PLZF)-RARalpha. SMRT was released from STAT5b-RARalpha/SMRT complexes by ATRA at 10(-6) M, whereas TRAM-1 became associated with STAT5b-RARalpha at 10(-7) M. The coiled-coil domain of STAT5b was required for formation of STAT5b-RARalpha homodimers, for the inhibition of RARalpha/RXRalpha transcriptional activity, and for stability of the STAT5b-RARalpha/SMRT complex. Thus, STAT5b-RARalpha contributes to myeloid maturation arrest by binding to RARE as either a homodimer or as a heterodimer with RXRalpha resulting in the recruitment of SMRT and inhibition of RARalpha/RXRalpha transcriptional activity. In addition, STAT5b-RARalpha and other APL fusion proteins may contribute to leukemogenesis by interaction with the STAT3 oncogene pathway.
UI - 11960906
AU - Kuerbitz SJ; Pahys J; Wilson A; Compitello N; Gray TA
TI - Hypermethylation of the imprinted NNAT locus occurs frequently in pediatric acute leukemia.
SO - Carcinogenesis 2002 Apr;23(4):559-64
AD - Department of Pediatrics and Department of Genetics, Case Western Reserve University and Ireland Cancer Center, Cleveland, OH 44109, USA.
Recent studies have demonstrated imprinting of the human neuronatin (NNAT) gene. NNAT maps to 20q11.2-q12, a region exhibiting loss of heterozygosity in acute myeloid leukemia and myelodysplastic/myeloproliferative disease. To investigate possible epigenetic dysregulation of genes in this region relevant to leukemogenesis, we analyzed methylation of the NNAT gene in normal tissues and in leukemias. We found a differential methylation pattern, typical of imprinted genes, at sites in the CpG island containing NNAT exon 1 in normal pituitary, peripheral blood cells and bone marrow-derived CD34-positive hematopoietic progenitor cells. Substantial or complete loss of the unmethylated NNAT allele was observed in leukemia cell lines and in 20 of 29 (69%) acute myeloid or lymphoid leukemia samples. While most highly expressed in brain, NNAT mRNA was also detected in normal hematopoietic progenitor cells and in leukemia cells exhibiting the normal methylation pattern, although not in hypermethylated leukemia cells. Demethylation by treatment of hypermethylated leukemia cells with 5-aza-2'-deoxycytidine resulted in reactivation of NNAT expression, concomitant with a reversion to the normal methylation pattern. The data demonstrate that hypermethylation of the NNAT locus is a frequent event in both myeloid and lymphoid acute leukemias of childhood. Aberrant hypermethylation of the NNAT locus suggests that the dysregulation of genes at 20q11.2-q12 in leukemia may be the result of epigenetic as well as genetic events.
UI - 12025826
AU - Cox R; Edwards AA
TI - Comments on the paper: Microsatellite instability in acute myelocytic leukaemia developed from A-bomb survivors--and related cytogenic data.
SO - Int J Radiat Biol 2002 May;78(5):443-5
UI - 11986943
AU - Pendino F; Sahraoui T; Lanotte M; Segal-Bendirdjian E
TI - A novel mechanism of retinoic acid resistance in acute promyelocytic leukemia cells through a defective pathway in telomerase regulation.
SO - Leukemia 2002 May;16(5):826-32
AD - INSERM U496, Centre G Hayem, Hopital Saint-Louis, 1 Avenue Claude Vellefaux, 75010 Paris, France.
Human telomerase, a cellular reverse transcriptase specifically activated in most malignant tumors and usually inactive in normal somatic cells, plays an important role in immortalization and tumorigenesis. Early reports have indicated that terminal differentiation of various cells is associated with a rapid inhibition of telomerase activity, preceded by a down-regulation of telomerase reverse transcriptase (hTERT) mRNA. Recently, we have shown that telomerase can be repressed by all-trans retinoic acid (ATRA) independently of terminal maturation during long-term ATRA treatment of the maturation-resistant promyelocytic leukemia cell line (NB4-R1), leading to shortening of telomeres and cell death, events overcome by ectopic hTERT expression. Here, we report the isolation of a variant of NB4-R1 cells (NB4-R1(SFD)), which bypasses this death step, because of a re-activated telomerase, despite the continuous presence of ATRA. While unresponsive to a long-term maturation independent regulation of telomerase by ATRA, these cells retain a functional pathway of telomerase down-regulation associated with retinoid-induced maturation. These findings reinforce the notion that two distinct pathways of telomerase regulation by retinoids co-exist in APL cells. Noteworthy, we show that the slow developing mechanism, that causes death of maturation-resistant cells, is subjected to a new type of retinoid-resistance as yet not understood.
UI - 11964319
AU - Milella M; Estrov Z; Kornblau SM; Carter BZ; Konopleva M; Tari A;
TI - Schober WD; Harris D; Leysath CE; Lopez-Berestein G; Huang Z; Andreeff M Synergistic induction of apoptosis by simultaneous disruption of the Bcl-2 and MEK/MAPK pathways in acute myelogenous leukemia.
SO - Blood 2002 May 1;99(9):3461-4
AD - Department of Blood and Marrow Transplantation, Section of Molecular Hematology and Therapy, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Recent studies suggest that the Bcl-2 and mitogen-activated protein kinase (MAPK) pathways together confer an aggressive, apoptosis-resistant phenotype on acute myelogenous leukemia (AML) cells. In this study, we analyzed the effects of simultaneous inhibition of these 2 pathways. In AML cell lines with constitutively activated MAPK, MAPK kinase (MEK) blockade by PD184352 strikingly potentiated the apoptosis induced by the small-molecule Bcl-2 inhibitor HA14-1 or by Bcl-2 antisense oligonucleotides. Isobologram analysis confirmed the synergistic nature of this interaction. Moreover, MEK blockade overcame Bcl-2 overexpression-mediated resistance to the proapoptotic effects of HA14-1. Most importantly, simultaneous exposure to PD184352 significantly (P =.01) potentiated HA14-1-mediated inhibition of clonogenic growth in all primary AML samples tested. These findings show that the Bcl-2 and MAPK pathways are relevant molecular targets in AML and that their concurrent inhibition could be developed into a new therapeutic strategy for this disease.
UI - 12040453
AU - Rex JH; Anaissie EJ; Boutati E; Estey E; Kantarjian H
TI - Systemic antifungal prophylaxis reduces invasive fungal in acute myelogenous leukemia: a retrospective review of 833 episodes of neutropenia in 322 adults.
SO - Leukemia 2002 Jun;16(6):1197-9
UI - 11921274
AU - Block AW; Carroll AJ; Hagemeijer A; Michaux L; van Lom K; Olney HJ; Baer
TI - MR Rare recurring balanced chromosome abnormalities in therapy-related myelodysplastic syndromes and acute leukemia: report from an international workshop.
SO - Genes Chromosomes Cancer 2002 Apr;33(4):401-12
AD - Clinical Cytogenetics Laboratory, Roswell Park Cancer Institute, Buffalo, New York 14263, USA. email@example.com
Seventy-seven patients were identified with Rare recurring (excluding 11q23, 21q22, inv(16), and t(15;17)) chromosome abnormalities among 511 patients with treatment-related myelodysplastic syndromes and acute leukemia accepted from centers in the United States, Europe, and Japan. The abnormality subsets included 3q21q26 (17 patients), 11p15 (17 patients), t(9;22)(q34;q11) (10 patients), 12p13 (9 patients), t(8;16)(p11;p13) (9 patients), and an "other" subset, which included t(6;9)(p23;q34) (3 patients), t(10;11)(p13;q13 approximately q21) (3 patients), t(1;17)(p36;q21) (2 patients), t(8;14)(q24;q32) (2 patients), t(11;19)(q13;q13) (2 patients), t(1;3)(p36;q21) (2 patients), and t(3;5)(q21;q31) (1 patient). Increased karyotypic complexity with additional balanced and unbalanced rearrangements was observed in 70% of cases. Among 54 cases with secondary abnormalities, chromosome 5 and/or 7 abnormalities were observed in 59%. The most frequent primary diseases were breast cancer (24 cases), Hodgkin disease (14 cases), non-Hodgkin lymphoma (10 cases), and de novo ALL (5 cases). Thirty-seven patients received alkylating agents plus topoisomerase II inhibitors with or without radiation therapy. The presenting diagnosis was t-AML in 47 cases, t-MDS in 23 cases (10 progressed to t-AML), and t-ALL in seven cases, five of whom had a t(9;22). The median latency time from initiation of original therapy to therapy-related disease diagnosis was quite long (69 months), and the overall median survival from the date of therapy-related disease diagnosis was very short (7 months). The 1-year survival rate was 34 +/- 7%, with no significant differences among subsets. Comparison with previously reported cases showed increased karyotypic complexity and adult presentation of pediatric-associated chromosome abnormalities. Copyright 2002 Wiley-Liss, Inc.
UI - 11911810
AU - Lamothe B; Aggarwal BB
TI - Ectopic expression of Bcl-2 and Bcl-xL inhibits apoptosis induced by TNF-related apoptosis-inducing ligand (TRAIL) through suppression of caspases-8, 7, and 3 and BID cleavage in human acute myelogenous leukemia cell line HL-60.
SO - J Interferon Cytokine Res 2002 Feb;22(2):269-79
AD - Cytokine Research Section, Department of Bioimmunotherapy, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030-4009, USA.
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is one of the latest members of the TNF superfamily known to induce apoptosis in a wide variety of tumor cells. Some cell types, however, are quite resistant to TRAIL. We investigated the effect of ectopic expression of Bcl-2 and Bcl-xL on TRAIL-induced apoptosis in human acute myelogenous leukemia HL-60 cells. We found that HL-60 cells, which express TRAIL receptors (also called death receptor, DR) DR4, DR5, and Dc (decoy) R2, are highly sensitive to TRAIL-induced cytotoxicity. Greater than 90% killing occurred within 24 h of TRAIL treatment. The expression of Bcl-2 and Bcl-xL, however, completely abolished the TRAIL-induced cytotoxic effects. Treatment of HL-60 cells with TRAIL induced caspase-8 activation within 2-4 h, but no activation could be seen in Bcl-2-expressing or Bcl-xL-expressing cells. TRAIL also induced cleavage of BID, which was also abolished by Bcl-2 and Bcl-xL. Similarly, TRAIL activated caspase-3 and caspase-7 in control cells but not in cells expressing Bcl-2 or Bcl-xL. Cleavage of the caspase-3 substrate poly(ADP-ribose) polymerase (PARP), was abrogated by ectopic expression of Bcl-2 and Bcl-xL. Inhibition of caspases by the pan-caspase inhibitor, benzyloxycarbonyl-valine-alanine-aspartate-fluoromethylketone (zVAD-fmk) abolished the TRAIL-induced apoptosis. Overall, these results indicate that TRAIL-induced apoptosis involves activation of caspase-8, caspase-7, caspase-3, and BID cleavage, and Bcl-2 and Bcl-xL prevents TRAIL-induced apoptosis by abrogating caspase activation and BID cleavage.
UI - 11920269
AU - Gu BW; Hu J; Xu L; Yan H; Jin WR; Zhu YM; Zhao WL; Niu C; Cao Q; Su XY;
TI - Gu J; Ying HY; Chen Y; Xiong SM; Shen ZX; Chen Z; Chen SJ Feasibility and clinical significance of real-time quantitative RT-PCR assay of PML-RARalpha fusion transcript in patients with acute promyelocytic leukemia.
SO - Hematol J 2001;2(5):330-40
AD - Shanghai Institute of Hematology, Key Laboratory of Human Genome Research, Ministry of Public Health and Shanghai Municipality, Rui-Jin Hospital, Shanghai Second Medical University, 197 Rui Jin Road II, Shanghai 200025, P.R. China.
INTRODUCTION: To study the relationship between the expression level of the PML-RARalpha fusion transcripts and the clinical status and efficiency of the therapy in acute promyelocytic leukemia (APL) patients, we applied a very sensitive and specific real-time Reverse Transcription Polymerase Chain Reaction (RT-PCR) system to quantify the dose of PML-RARalpha fusion transcripts in a series of APL patients at distinct disease stages. MATERIALS AND METHODS: A total of 31 APL patients (19 males and 12 females; aged from 8 to 74 years) from eight hospitals in Shanghai were analysed. Real-time Quantitative RT-PCR was used to measure the normalized dose (DoseN) of PML-RARalpha fusion transcripts. RESULTS: A wide range of PML-RARalpha DoseN above 1 x 10(3) was noted in 25 newly diagnosed patients. PML-RARalpha DoseN was significantly decreased after remission induction with ATRA, ATRA/chemotherapy or As2O3 and further reduced after consolidation. The fact that all patients with long disease free survival had a constantly low PML-RARalpha DoseN below 2 x 10(2) and a higher level predicted impending relapse suggests that this value could serve as a 'threshold' for molecular remission. PML-RARalpha DoseN was also of prognostic value in a group of relapsed patients, since good response to As2O3 reinduction was accompanied by a remarkable reduction of fusion transcript level, whereas patients with high PML-RARalpha Dose(N) after the second CR tended to relapse again rapidly. CONCLUSION: These results confirm that real-time RT-PCR assay for PML-RARalpha transcripts in APL patients is useful in reflecting leukemic burden, assessing response to treatment and indicating the ultimate clinical outcome or curability of disease.
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