Bone Marrow Cells From Low-Risk Myelodysplastic Syndrome Patients Show Features of Enhanced Autophagy

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4961-4961
Author(s):  
Yuan-yuan Wang ◽  
Zi-Xing Chen ◽  
Jian-nong Cen ◽  
Hong-jie Shen ◽  
Xiao-fei Qi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndrome ◽  
Mononuclear Cells ◽  
Bone Marrow Cells ◽  
Conflicts Of Interest ◽  
Low Risk ◽  
Beclin 1 ◽  
Healthy Controls ◽  
Aberrant Expression ◽  
Marrow Cells

Abstract Abstract 4961 Myelodysplastic syndrome (MDS) is a preneoplastic condition that frequently develops into overt acute myeloid leukemia (AML). Beclin 1, a gene plays an important role in autophagy, has been recognized as a tumour suppressor. The aberrant expression of Beclin 1 has been correlated to the development and progression of cancer. However, The function and expression of Beclin 1 in MDS is largely unexplored. The present study aimed to investigate Beclin 1 expression and its correlation with IPSS in bone marrow cells from Patients with Low-Risk MDS. We have analyzed the expression of Beclin 1 in BM mononuclear cells (BMMNCs) from patients of Low-Risk MDS (31 cases), 22 AML(22 cases) and healthy control (9 cases) by quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR), immunofluorescence and western blot analysis. The expression level of Beclin 1 mRNA is significantly higher in BMMNCs in patients with Low-Risk MDS(mean± SD=6.26±4.87) when compared to healthy controls (mean± SD= 1.52±1.37), and the IPSS score was negatively correlated with the percentage of Beclin 1 positive cells. A markedly decreased expression of Beclin 1 was observed in AML (mean± SD=1.12±1.04) compared with healthy controls. The amount of Beclin 1 protein determined by either western blotting or immunofluorescence was markedly increased in MDS compared with that in controls (P<0.05). These results indicated that the cells from Patients with Low-Risk Myelodysplasia show features of enhanced autophagy, suggesting that the biological phenotype of autophagy, in addition to apoptosis and senescence, may also participate in the development of MDS and its progression to AML. Disclosures: No relevant conflicts of interest to declare.

Expression of dlk1 in the Bone Marrow Cells of Patients with Myelodysplastic Syndrome and Its Clinical Significance

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5042-5042
Author(s):  
Zonghong Shao ◽  
Lanzhu Yue ◽  
Rong Fu ◽  
Lijuan Li ◽  
Erbao Ruan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Early Diagnosis ◽  
Myelodysplastic Syndrome ◽  
Bone Marrow Cells ◽  
Conflicts Of Interest ◽  
Rt Pcr ◽  
Normal Controls ◽  
Lower Expression ◽  
Bone Marrow Blasts ◽  
Marrow Cells

Abstract Abstract 5042 Objective To investigate the expression of dlk1 gene (delta-like 1) in the bone marrow cells of patients with Myelodysplastic syndrome (MDS), and explore the molecular marker for early diagnosis of MDS. Methods The expression of dlk1 mRNA in the bone marrow cells of cases with MDS, AML and normal controls were measured by RT-PCR, aiming to search for the cytogenetic marker of MDS malignant clone. Results The expression of dlk1 mRNA in bone marrow cells of MDS patients (0.7342±0.3652) was significantly higher than that of normal controls (0.4801±0.1759) (P<0.05), and was significantly positively correlated with the proportion of bone marrow blasts(r=0.467,P<0.05). The expression of dlk1 mRNA significantly increased as the subtype of MDS advanced (P<0.05). Patients with abnormal karyotypes displayed significantly higher expression of dlk1 mRNA (0.9007±0.4334) than those with normal karyotypes (0.6411±0.2630) (P<0.05). Patients with higher expression of dlk1(≥0.8) presented significantly higher malignant clone burden (0.4134±0.3999) than those with lower expression (<0.8) of dlk1 (0.1517±0.3109) (P<0.05). Conclusion dlk1 gene was highly expressed in MDS patients, which increased as the subtype of MDS advanced. The expression of dlk1 mRNA was significantly positively correlated with the proportion of bone marrow blasts. High expression of dlk1 gene suggests high malignant clone burden of MDS. Disclosures: No relevant conflicts of interest to declare.

A Patient-Derived EZH2 Mutant Induces MDS-like Diseases with Derepressed ABCG2 Expression in Mice

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4116-4116
Author(s):  
Kimihito Cojin Kawabata ◽  
Daichi Inoue ◽  
Jiro Kitaura ◽  
Yuka Harada ◽  
Susumu Goyama ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Target Genes ◽  
De Novo ◽  
Bone Marrow Cells ◽  
Conflicts Of Interest ◽  
Short Form ◽  
Physiological Role ◽  
Aberrant Expression ◽  
H3k27 Trimethylation ◽  
Marrow Cells

Abstract A histone H3 Lysine 27 (H3K27)-methyltransferase, enhancer of zeste homolog 2(EZH2) is known as a tumor-associated gene. Physiological role of EZH2 is an enzymatic component of polycomb repressive complex 2 (PRC2) to inhibit expression of target genes. While EZH2 plays oncogenic roles by repressing the expression of tumor suppressors in solid tumors and some lymphomas, it plays rather tumor-suppressive roles in myeloid malignancies. We have generated a short-form EZH2 that lacks the catalytic SET domain (EZH2-dSET). Using this EZH2 mutant we could produce serially transplantable MDS-like diseases. Microarray analysis using the MDS-like bone marrow cells enabled us to identify novel targets of EZH2 in MDS tumorigenesis, including ATP-binding cassette (ABC) transporters. Derepression of Abcg2 via decreased H3K27-trimethylation was confirmed. Retroviral transduction of EZH2-dSET to MDS-like cell lines increased surface ABCG2-high populations and those cells functioned to exclude anticancer drugs as expected. Intriguingly, with Abcg2 expression alone, primary bone marrow cells could produce an MDS-like cytopenic disease in our BMT model. In our clinical specimens, ABCG2 high expressions were observed in MDS samples but not in de novo AML and CML samples. In two MDS patients, ABCG2 expression decreased along with leukemic transformation. Interestingly, two out of 33 MDS patients with extremely high expression of ABCG2 harbored the same U2AF1 mutation (Q157P). In addition, somatic mutations of EZH2 and those of either U2AF1 or SRSF2 were mutually exclusive in all investigated cases. Interestingly, U2AF1 mutants (S34F and Q157P) reduced EZH2 expression, leading the derepression of ABCG2 via decreased H3K27-trimethylation. These results indicate a link between U2AF1 mutations and ABCG2 expression via disrupted EZH2. In conclusion, different mechanisms are supposed to converge at dysregulated EZH2 in MDS. And a short form of EZH2 upregulates ABCG2 expression resulting in MDS advancing to secondary leukemia. Thus, either mutations affecting the EZH2 function or mutations of EZH2 itself could play an important role in MDS, and one of the downstream targets of EZH2 suppression in MDS pathogenesis is aberrant expression of ABCG2. Disclosures No relevant conflicts of interest to declare.

Oxidative DNA damage in bone marrow cells of patients with low-risk myelodysplastic syndrome

2009 ◽  
Vol 33 (2) ◽  
pp. 340-343 ◽  
Author(s):  
Bozena Novotna ◽  
Yana Bagryantseva ◽  
Magda Siskova ◽  
Radana Neuwirtova
Keyword(s):  
Bone Marrow ◽  
Dna Damage ◽  
Myelodysplastic Syndrome ◽  
Oxidative Dna Damage ◽  
Bone Marrow Cells ◽  
Low Risk ◽  
Marrow Cells

scholarly journals Analysis of interferon-inducible genes in cells of chronic myeloid leukemia patients responsive or resistant to an interferon-alpha treatment

Blood ◽  
1990 ◽  
Vol 76 (11) ◽  
pp. 2337-2342
Author(s):  
IM Clauss ◽  
B Vandenplas ◽  
MG Wathelet ◽  
C Dorval ◽  
A Delforge ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chronic Myeloid Leukemia ◽  
Interferon Alpha ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Bone Marrow Cells ◽  
Healthy Controls ◽  
Ifn Alpha ◽  
Inducible Genes ◽  
Marrow Cells

Recombinant human interferon-alpha (IFN-alpha) can induce a hematologic remission in patients with chronic myeloid leukemia. However, some patients are resistant and others develop late resistance to the IFN- alpha treatment. To understand the molecular mechanism of this resistance, we have analyzed the expression of 10 IFN-inducible genes in the cells of three resistant patients, two responsive patients, and six healthy controls. Northern blot hybridizations showed that all the genes were induced in in vitro IFN-alpha treated peripheral blood cells of the patients and healthy controls. These genes were also inducible in peripheral blood and bone marrow cells of two out of two resistant patients administered an injection of IFN-alpha. We conclude that the resistance to the IFN-alpha treatment of the chronic myeloid leukemia patients we studied is not due to (1) the absence of induction of any of the 10 IFN-inducible genes we studied, including the low-molecular- weight 2′-5′oligoadenylate synthetase; (2) the presence of an antagonist of IFN-alpha in the peripheral blood or bone marrow cells; and (3) the presence of neutralizing anti-IFN-alpha antibodies.

scholarly journals Analysis of CNV in the Genomes of the Marrow Cells of the Patients with AML Revealed That High Numbers of Aberrations Associate with Better Survival and Deletions with the Aberrant Expression of CD19 in the Leukemic Blasts

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5164-5164
Author(s):  
Emilia Jaskula ◽  
Janusz Lange ◽  
Monika Mordak-Domagala ◽  
Mariola Sedzimirska ◽  
Marta Lemieszewska ◽  
...  
Keyword(s):  
Chromatin Structure ◽  
Bone Marrow Cells ◽  
Conflicts Of Interest ◽  
Hidden Markov ◽  
Aberrant Expression ◽  
Knowing That ◽  
Segmentation Algorithms ◽  
The Mean ◽  
Cd19 Expression ◽  
Marrow Cells

In our previous study (Jaskula et al., Blood 2017 130:1420) we reported that the number of CNVs within the KANSL1 gene was associated with the phenotype of AML. In the present study we looked at the presence of CNV across the whole genome. One hundred and twenty seven AML patients (diagnosed according to the FAB/WHO criteria, F/M=62/65, age median: 57, range: 21 - 84 years) were included to the present study. The patients were genetically analysed including GTG karyotyping and/or FISH for X or Y deletion, inv (3), -5/5q-, -7/7q-,+8, MLL, RUNX1, PML/RARA or RARA, inv(16). In all patients the microarray analysis of the bone marrow cells having blasts cells (median value 56%) at diagnosis Agilent - Catalog Agilent Cancer CGH+SNP 180K (74 patients) or Roche - WG Catalog NimbleGene 12x270K (53 patients) microarrays were employed and the results were analysed with the use the Partek software employing the Partek Hidden Markov Model (HMM) and segmentation algorithms. Results: The number of CNV in M0 AML marrow cells was significantly lower (median: 0 aberration), as compared to secondary to MDS AML (median: 4.5 aberrations, p=0.006). Patients with AML subtypes from M1 to M6 had higher number of CNV amplifications (median: 2) as compared to the patients with minimally differentiated blasts (M0, median: 0 amplifications, p=0.030). Knowing that (i) changes in the chromatin structure may be associated with the CNV prevalence within the genome (Gheldof et al., PLoS One. 2013 Nov 12;8(11):e79973) and (ii) the aberrant expression of CD19 in AML blasts results from the chromatin structure variations (Walter et al., Oncogene. 2010 May 20;29(20):2927-37) we looked at the presence of association between the numbers of CNV and the presence of the aberrant CD19 expression in the leukemic blasts. It appeared that 11 AML patients having aberrant expression of CD19 (within whom 4 had t(8:21)) had more frequently CNV deletions than those lacking this aberrant expression (median: 2 vs 1 deletions, p=0.018, HMM algorithm). Having the survival curves of the patients plotted accordingly to the high and low numbers of CNV, the situation is more complex and shows that: the patients having higher numbers of CNV aberrations (exceeding the mean of the whole group +SD) enjoyed better survival (20% vs 11%, p=0.090) when segmentation algorithm was employed. HMM analysis also suggested that the higher values of CNV (amplifications, exceeding the mean of the whole group +SD) was associated with better 5-year survival as compared to those with low numbers (42% vs 20%, ns). The aberrant expression of CD19 analysis was associated with higher numbers of deletions (see above) and with better 5-year survival than those lacking this aberrant expression (45% vs 20%, p=0.064). In conclusion, the prevalence of CNV within the genome shapes the phenotype of the leukemia and facilitates the survival. Disclosures No relevant conflicts of interest to declare.

scholarly journals Mutational Characteristics and Changing Pattern from Idiopathic Cytopenia of Undetermined Significance to High-Risk Myelodysplastic Syndrome Stratified By IPSS-R

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3009-3009
Author(s):  
Eun-Ji Choi ◽  
Young-Uk Cho ◽  
Seongsoo Jang ◽  
Chan-jeoung Park ◽  
Han-Seung Park ◽  
...  
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Myelodysplastic Syndrome ◽  
Rna Splicing ◽  
Conflicts Of Interest ◽  
Low Risk ◽  
International Prognostic Scoring System ◽  
Intermediate Risk ◽  
Sequencing Data ◽  
Undetermined Significance

Background: Unexplained cytopenia comprises a spectrum of hematological diseases from idiopathic cytopenia of undetermined significance (ICUS) to myelodysplastic syndrome (MDS). Revised International Prognostic Scoring System (IPSS-R) is the standard tool to assess risk in MDS. Here, we investigated the occurrence, characteristics, and changing pattern of mutations in patients with ICUS and MDS stratified by IPSS-R score. Methods: A total of 211 patients were enrolled: 73 with ICUS and 138 with MDS. We analyzed the sequencing data of a targeted gene panel assay covering 141 genes using the MiSeqDx platform (Illumina). The lower limit of variant allele frequency (VAF) was set to 2.0% of mutant allele reads. Bone marrow components were assessed for the revised diagnosis according to the 2016 WHO classification. Lower-risk (LR) MDS was defined as those cases with very low- or low-risk MDS according to the IPSS-R. Higher-risk (HR) MDS was defined as those cases with high- or very high-risk MDS according to the IPSS-R. Results: Patients with ICUS were classified as very low-risk (39.7%), low-risk (54.8%), and intermediate-risk (5.5%) according to the IPSS-R. Patients with MDS were classified as LR (35.5%), intermediate-risk (30.4%), and HR (34.1%). In the ICUS, 28 (38.4%) patients carried at least one mutation in the recurrently mutated genes in MDS (MDS mutation). The most commonly mutated genes were DNMT3A (11.0%), followed by TET2 (9.6%), BCOR (4.1%), and U2AF1, SRSF2, IDH1 and ETV6 (2.7% for each). IPSS-R classification was not associated with mutational VAF and the number of mutations in ICUS. In the 49 LR MDS, 28 (57.1%) patients carried at least one MDS mutation. The most commonly mutated genes were SF3B1 (20.4%), followed by TET2 (12.2%), U2AF1 (10.2%), DNMT3A (10.2%), ASXL1 (10.2%), and BCOR (6.1%). Higher VAF and number of mutations were observed in LR MDS compared to ICUS patients. In the 42 intermediate-risk MDS, 27 (64.3%) patients carried at least one MDS mutation. The most commonly mutated genes were ASXL1 (23.8%), followed by TET2 (21.4%), RUNX1 (16.7%), U2AF1 (14.3%), DNMT3A (14.3%), SF3B1 (9.5%), and SRSF2, BCOR, STAG2 and CBL (7.1% for each). In the 47 HR MDS, 36 (76.6%) patients carried at least one MDS mutation. The most commonly mutated genes were TET2 (25.5%), followed by DNMT3A (14.9%), TP53 (14.9%), RUNX1 (12.8%), U2AF1 (10.6%), ASXL1 (10.6%), and SRSF2 and KRAS (6.4% for each). As the disease progressed, VAF and number of the MDS mutations gradually increased, and mutations involving RNA splicing, histone modification, transcription factor or p53 pathway had a trend for increasing frequency. Specifically, ASXL1, TP53, and RUNX1 mutations were the most striking features in patients with advanced stage of the disease. Cohesin mutations were not detected in ICUS, whereas these mutations were detected at a relatively high frequency in HR MDS. Our data were summarized in Table 1. Conclusions: We demonstrate that on disease progression, MDS mutations are increased in number as well as are expanded in size. Furthermore, a subset of mutations tends to be enriched for intermediate- to HR MDS. The results of this study can aid both diagnostic and prognostic stratification in patients with unexpected cytopenia. In particular, characterization of MDS mutations can be useful in refining bone marrow diagnosis in challenging situations such as distinguishing LR MDS from ICUS. Disclosures No relevant conflicts of interest to declare.

Anti-fibrotic potential of human umbilical cord mononuclear cells and mouse bone marrow cells in CCl 4 - induced liver fibrosis in mice

2017 ◽  
Vol 89 ◽  
pp. 1378-1386 ◽  
Author(s):  
Nageh Ahmed Elmahdy ◽  
Samia Salem Sokar ◽  
Mohamed Labib Salem ◽  
Naglaa Ibrahim Sarhan ◽  
Sherin Hamed Abou-Elela
Keyword(s):  
Bone Marrow ◽  
Liver Fibrosis ◽  
Umbilical Cord ◽  
Mononuclear Cells ◽  
Bone Marrow Cells ◽  
Human Umbilical Cord ◽  
Mouse Bone Marrow ◽  
Mouse Bone Marrow Cells ◽  
Marrow Cells

scholarly journals Differential effects of nitric oxide on erythroid and myeloid colony growth from CD34+ human bone marrow cells

Blood ◽  
1996 ◽  
Vol 87 (3) ◽  
pp. 977-982 ◽  
Author(s):  
PJ Shami ◽  
JB Weinberg
Keyword(s):  
Bone Marrow ◽  
Mononuclear Cells ◽  
Bone Marrow Cells ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Monocytic Differentiation ◽  
Colony Forming Unit ◽  
Normal Human ◽  
Normal Human Bone Marrow ◽  
Marrow Cells

Nitric oxide (NO) is a reactive molecule with numerous physiologic and pathophysiologic roles affecting the nervous, cardiovascular, and immune systems. In previous work, we have demonstrated that NO inhibits the growth and induces the monocytic differentiation of cells of the HL- 60 cell line. We have also demonstrated that NO inhibits the growth of acute nonlymphocytic leukemia cells freshly isolated from untreated patients and increases monocytic differentiation antigens in some. In the present work, we studied the effect of NO on the growth and differentiation of normal human bone marrow cells in vitro. Mononuclear cells isolated from human bone marrow were cultured in semisolid media and treated with the NO-donating agents sodium nitroprusside (SNP) or S- nitroso-acetyl penicillamine (SNAP) (0.25 to 1 mmol/L). Both agents decreased colony-forming unit-erythroid (CFU-E) and colony-forming unit- granulocyte macrophage (CFU-GM) formation by 34% to 100%. When CD34+ cells were examined, we noted that these cells responded to SNP and SNAP differently than did the mononuclear cells. At a concentration range of 0.25 to 1 mmol/L, SNP inhibited the growth of CFU-E by 30% to 75%. However, at the same concentration range, SNP increased the number of CFU-GM by up to 94%. At concentrations of 0.25 to 1 mmol/L, SNAP inhibited the growth of CFU-E by 33% to 100%. At a concentration of 0.25 mmol/L, SNAP did not affect CFU-GM. At higher concentrations, SNAP inhibited the growth of CFU-GM. Although SNP increased intracellular levels of cGMP in bone marrow cells, increasing cGMP in cells by addition of 8-Br-cGMP (a membrane permeable cGMP analogue) did not reproduce the observed NO effects on bone marrow colonies. These results demonstrate that NO can influence the growth and differentiation of normal human bone marrow cells. NO (generated in the bone marrow microenvironment) may play an important role modulating the growth and differentiation of bone marrow cells in vivo.

FLIP (Long) and FLIP (Short) Expression in Bone Marrow Cells in Patients with Myelodysplastic Syndrome: Correlation with FAB and WHO Classification.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4926-4926
Author(s):  
Paula Campos ◽  
Fabiola Traina ◽  
Adriana Duarte ◽  
Bruno Benites ◽  
Marcelo Brandao ◽  
...  
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Myelodysplastic Syndrome ◽  
Mrna Expression ◽  
Who Classification ◽  
Fas Ligand ◽  
Low Risk ◽  
World Health ◽  
Caspase 8 ◽  
Marrow Cells

Abstract The paradox of peripheral cytopenias despite of normo/hypercellular marrow in myelodysplastic syndrome (MDS) has been ascribed to excessive intramedullary hematopoietic cell apoptosis. Several apoptosis-inducing systems, including Fas/Fas ligand and TNF-related apoptosis-inducing ligand (TRAIL) and its receptors, are upregulated in MDS. FLIP (FLICE (FAS-associated death-domain-like IL-1β-converting enzyme)-inhibitory protein) was identified as a FAS and TRAIL signal inhibitor. The largest variant FLIPLong (FLIPL) was originally characterized as a molecule with inhibitory activity on caspase-8. The short splice form termed FLIPShort (FLIPS) has also been characterized as a potent (TRAIL-induced) apoptosis inhibitor. However, whereas FLIPL and FLIPS have been described as death receptor pathway inhibitors, recent data suggest that physiologically, FLIPL may have caspase-8-activating properties. This study aims to characterize the expression of FLIPL and FLIPS based on mRNA, by Real-time quantitative PCR, in marrow cells from MDS patients and to correlate the expression with French-American-British (FAB) and World Health Organization (WHO) classification. For each sample, results were first calculated as a ratio of the total transcript number of FLIPL or FLIPS and the total transcript number of the endogenous reference gene (β-actin) to obtain a normalized target value. Transcript ratios of each sample were normalized against the respective ratio of a pool of 6 normal bone marrow donors (NBM), and the ratio between the two was used as measure for the relative FLIPL or FLIPS level. We hypothesized that FLIPL and FLIPS expression differed between low and high risk of MDS. Marrow aspirates were obtained from 6 NBM and 16 patients with MDS out of treatment (7 males, 9 females; 23–78 (median 64) yo). The National Ethical Committee Board approved this study, informed-written consent was obtained from all patients and donors. According to FAB classification, patients were distributed as: 10 RA, 2 RARS and 4 RAEB. According to WHO classification: 10 RCMD, 2 RCMD-RS, 3 RAEB-1 and 1 RAEB-2. FLIPS mRNA expression were significantly higher in high risk DS according to FAB and WHO classification; RA/RARS compared with AREB (0.08 [0.0–2.3] vs 0.67 [0.36–1.54]; P = 0.03); RCMD and RCMD-RS compared with RAEB-1 and RAEB-2 (0.08 [0.0–2.3] vs 0.67 [0.36–1.54]; P = 0.03). However, FLIPL mRNA expression also tended to be higher in high risk MDS according to FAB and WHO classification, though not significantly different: RA/RARS compared with AREB (1.18 [0.06–3.43] vs 1.65 [0.51–3.63]; P = 0.46); RCMD and RCMD-RS compared with RAEB-1 and RAEB-2 (1.18 [0.06–3.43] vs 1.65 [0.51–3.63]; P = 0.46). Lower FLIPS level in low risk MDS marrows, in addition to the well described upregulation of extracellular proapoptotic signals, would explain the increased susceptibility of hematopoietic cells in low risk MDS marrow to death-inducing stimuli. The fact that FLIPL expression did not differ according to FAB and WHO classification could be related to the hypothesis that FLIPL may have caspase-8-activating properties rather than anti-apoptotic activity. Differential regulation of FLIPL and FLIPS according to risk groups in MDS patients might result in different rates of apoptosis. Further studies are needed to elucidate the mechanisms controlling and regulating FLIP expression in normal and malignant hemopoietic cells.

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