scholarly journals Requirement of c-Myb for p210BCR/ABL-dependent transformation of hematopoietic progenitors and leukemogenesis

Blood ◽  
2008 ◽  
Vol 111 (9) ◽  
pp. 4771-4779 ◽  
Author(s):  
Maria Rosa Lidonnici ◽  
Francesca Corradini ◽  
Todd Waldron ◽  
Timothy P. Bender ◽  
Bruno Calabretta
Keyword(s):  
Median Survival ◽  
Colony Formation ◽  
Myeloid Leukemia ◽  
Blast Crisis ◽  
Cyclin B1 ◽  
Myelogenous Leukemia ◽  
Hematopoietic Progenitors ◽  
Myb Gene ◽  
Blast Cells ◽  
Marrow Cells

Abstract The c-Myb gene encodes a transcription factor required for proliferation and survival of normal myeloid progenitors and leukemic blast cells. Targeting of c-Myb by antisense oligodeoxynucleotides has suggested that myeloid leukemia blasts (including chronic myelogenous leukemia [CML]–blast crisis cells) rely on c-Myb expression more than normal progenitors, but a genetic approach to assess the requirement of c-Myb by p210BCR/ABL-transformed hematopoietic progenitors has not been taken. We show here that loss of a c-Myb allele had modest effects (20%-28% decrease) on colony formation of nontransduced progenitors, while the effect on p210BCR/ABL-expressing Lin− Sca-1+ and Lin− Sca-1+Kit+ cells was more pronounced (50%-80% decrease). Using a model of CML-blast crisis, mice (n = 14) injected with p210BCR/ABL-transduced p53−/−c-Mybw/w marrow cells developed leukemia rapidly and had a median survival of 26 days, while only 67% of mice (n = 12) injected with p210BCR/ABL-transduced p53−/−c-Mybw/d marrow cells died of leukemia with a median survival of 96 days. p210BCR/ABL-transduced c-Mybw/w and c-Mybw/d marrow progenitors expressed similar levels of the c-Myb–regulated genes c-Myc and cyclin B1, while those of Bcl-2 were reduced. However, ectopic Bcl-2 expression did not enhance colony formation of p210BCR/ABL-transduced c-Mybw/d Lin−Sca-1+Kit+ cells. Together, these studies support the requirement of c-Myb for p210BCR/ABL-dependent leukemogenesis.

Hemophagocytosis or emperipolesis by lymphoblast after rapid transformation of chronic myeloid leukemia

2021 ◽  
Vol 2 (4) ◽  
Author(s):  
João Lucas Cruz-Souza ◽  
◽  
Fernanda Paula de Carvalho ◽  
Márcio Antonio Wanderley de Melo ◽  
Edinalva Pereira Leite ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myeloid Leukemia ◽  
Outpatient Visit ◽  
Clinical Findings ◽  
Myelogenous Leukemia ◽  
Bone Marrow Aplasia ◽  
Hla Dr ◽  
Consolidation Phase ◽  
Blast Cells ◽  
Rapid Transformation

A Male, 11-Years-Old, Admitted In March 2019 With Chronic myelogenous leukemia (CML) in treatment with Imatinib. Three months after diagnosis in outpatient visit was observed increase of splenomegaly and appearing of inguinal and cervical adenomegalies. Bone marrow apiration revealed 70% of blasts, some of them with hemophagocytosis (Figure 1). The immunophenotyping showed blasts positive for CD10, CD19, CD20, CD22, CD79a, CD45, HLA-DR, indicating transformation to B precursors ALL. Bone marrow karyotype was 46,XY,t(9;22), FISH (BCR-ABLES probe) confirmed rearrangement with p210. The patient was treated with higher dose of Imatinib (600 mg/m²), but evolved with bone marrow aplasia and infectious process, being then reajusted to 400 mg/m² with clinical and hematologic improvement. After 30 days had disease aggravation and resistance to Imatinib. The patient initiated EsPh-ALL 2009 protocol, but in D33 with no remission of disease continued with protocol. In September, during consolidation phase evolved with Central Nervous System infiltration and disease persistence, dying for disease in progress. This patient had no clinical findings of Hemophagocytic Lymphohistiocytosis (HLH) and bone marrow cytology showed the several hematopoietic cells inside blast cells.

Constitutive expression of SOCS3 confers resistance to IFN-α in chronic myelogenous leukemia cells

Blood ◽  
2002 ◽  
Vol 100 (8) ◽  
pp. 2926-2931 ◽  
Author(s):  
Ikuya Sakai ◽  
Kazuto Takeuchi ◽  
Hayato Yamauchi ◽  
Hirosi Narumi ◽  
Shigeru Fujita
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Chronic Myelogenous Leukemia ◽  
Blast Crisis ◽  
Constitutive Expression ◽  
Myelogenous Leukemia ◽  
Cytokine Signaling ◽  
Interferon Α ◽  
Socs3 Expression ◽  
Blast Cells

Because suppressor of cytokine signaling (SOCS) proteins are negative regulators of cytokine-induced signaling, it has been hypothesized that aberrant SOCS expression confers resistance against cytokine therapy. This study reports on the constitutive expression of SOCS3 in most chronic myelogenous leukemia (CML) cell lines, which are resistant to treatment with interferon α (IFN-α). In contrast, the KT-1/A3 cell line, in which constitutive expression of SOCS3 is barely detectable, is sensitive to IFN-α treatment. Forced expression of SOCS3 in the KT-1/A3 cell line confers resistance to IFN-α treatment. Furthermore, most of the blast cells from patients in CML blast crisis, which are usually resistant to IFN-α therapy, showed constitutive expression of SOCS3. These findings indicate that constitutive SOCS3 expression affects the IFN-α sensitivity of CML cell lines and blast cells from patients with CML blast crisis.

scholarly journals Expression of axl, a transforming receptor tyrosine kinase, in normal and malignant hematopoiesis

Blood ◽  
1994 ◽  
Vol 84 (6) ◽  
pp. 1931-1941 ◽  
Author(s):  
A Neubauer ◽  
A Fiebeler ◽  
DK Graham ◽  
JP O'Bryan ◽  
CA Schmidt ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Intracellular Signaling ◽  
Myeloid Leukemia ◽  
Blast Crisis ◽  
Chronic Phase ◽  
Lymphocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Hematopoietic Tissue ◽  
Blood Leukocytes

Abstract We previously reported the cloning, and characterization of a receptor tyrosine kinase, axl, from two patients with chronic myelogenous leukemia. Herein, we describe the expression pattern of axl in normal and malignant hematopoietic tissue axl message is detected in normal human bone marrow but not significantly in normal blood leukocytes. Cell separation experiments showed that axl is expressed in hematopoietic CD34+ progenitor and marrow stromal cells, at low levels in peripheral monocytes, but not in lymphocytes or granulocytes. Consistent with the normal pattern of axl expression, axl RNA was found predominantly in diseases of the myeloid lineage: 39 of 66 (59%) patients with myeloproliferative disorders (acute myeloid leukemia, chronic myeloid leukemia (CML) in chronic phase, CML in myeloid blast crisis, and myelodysplasia) showed significant axl transcription, as compared with 1 of 45 (2%) lymphoid leukemias (chronic lymphocytic leukemia, acute lymphocytic leukemia, and CML in lymphoid blast crisis). Treatment of K562 cells with the phorbol ester, 12-O- tetradecanoylphorbol-13-acetate (TPA), administration of interferon alpha (IFN alpha) to normal monocytes, and treatment of U937 cells with TPA and IFN tau significantly induced axl expression, supporting a role for this kinase in the intracellular signaling of myeloid cells through a variety of biochemical pathways. These results suggest that the axl kinase may be operative in normal and malignant myeloid biology.

scholarly journals Acute- and chronic-phase chronic myelogenous leukemia colony-forming units are highly sensitive to the growth inhibitory effects of c-myb antisense oligodeoxynucleotides

Blood ◽  
1992 ◽  
Vol 79 (8) ◽  
pp. 1956-1961 ◽  
Author(s):  
MZ Ratajczak ◽  
N Hijiya ◽  
L Catani ◽  
K DeRiel ◽  
SM Luger ◽  
...  
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Colony Formation ◽  
Ex Vivo ◽  
Blast Crisis ◽  
Chronic Phase ◽  
Myelogenous Leukemia ◽  
Antisense Oligodeoxynucleotides ◽  
Rt Pcr ◽  
Colony Forming Units

Abstract We have previously demonstrated that malignant hematopoietic colony- forming units (CFUs) may be purged from normal CFU by exposure to c-myb antisense oligodeoxynucleotides (oligomers). This novel strategy appeared particularly promising for patients with chronic myelogenous leukemia (CML) in blast crisis, since in some cases complete elimination of bcr-abl-expressing cells was accomplished. We have examined 11 additional patients, including seven in chronic phase, in order to extend these initial observations. We sought in particular to determine if elimination of bcr-abl-expressing clones was a usual event. Exposure of CML cells to c-myb antisense oligomers resulted in inhibition of CFU-granulocyte, macrophage (CFU-GM)-derived colony formation in eight of 11 (73%) cases evaluated. Inhibition was antisense sequence-specific, dose-dependent, ranged between 58% and 93%, and was statistically significant (P less than or equal to .03) in seven of the eight cases. In two cases, CFU-granulocyte, erythrocyte, monocyte, megakaryocyte (CFU-GEMM)-derived colony formation was also examined and found to be inhibited by the c-myb antisense oligomers in a sequence-specific manner. To determine whether CML CFU had been reduced or eliminated after exposure to the antisense oligomers, we examined cells in the residual colonies for bcr-abl mRNA expression using a reverse transcription-polymerase chain reaction detection technique (RT-PCR). Eight cases were evaluated and in each case where antisense myb inhibited growth, bcr-abl expression as detected by RT- PCR was either greatly decreased or nondetectable. No residual leukemic CFU were demonstrable on replating of treated cells. These results suggest that c-myb antisense oligomers substantially inhibit the growth and survival of CML CFU in both chronic and blast phase of disease. They may therefore prove useful for both ex vivo and in vivo treatment of CML.

FTY720, a New and Alternative Strategy for Treating Blast Crisis CML and Ph1 ALL Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 288-288 ◽  
Author(s):  
Ramasamy Santhanam ◽  
Paolo Neviani ◽  
Anna Eiring ◽  
Joshua Oaks ◽  
Mario Notari ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Median Survival ◽  
Blast Crisis ◽  
Myelogenous Leukemia ◽  
Current Therapy ◽  
Solid Organ ◽  
In Vivo Models

Abstract Blast crisis chronic myelogenous leukemia (CML-BC) and Philadelphia chromosome positive (Ph1) acute lymphoblastic leukemia (ALL) are two fatal BCR/ABL-driven leukemias against which the current therapy with Abl kinase inhibitors fails to induce a long-term response, as the majority of patients are either refractory or relapse after a few months of treatment. We recently reported that functional loss of the PP2A tumor suppressor occurs during CML disease progression and that restoration of PP2A activity impairs in vitro and in vivo BCR/ABL leukemogenesis. Here we assessed the therapeutic potential of the PP2A activator FTY720 in CML-BC and Ph1 ALL patient cells and in in vitro and in vivo models of these BCR/ABL+ leukemias. FTY720 (500 nM-2.5 mM) induces caspase-dependent apoptosis (70–98% annexin V+) and impairs the clonogenic potential (70–95% inhibition) of imatinib/dasatinib-sensitive and -resistant (T315I) p210 and p190 BCR/ABL-expressing myeloid and lymphoid progenitor cell lines (Ph1 K562, 32D-p210BCR/ABL, 32D-p210(T315I)BCR/ABL and BaF3-p190BCR/ABL), respectively, and of primary bone marrow CML-BCCD34+ (n=11) and Ph1 ALLCD34+/CD19+ (n=12) patients cells. Interestingly the cytokine (IL-3 or IL-7)-dependent growth and differentiation of normal CD34+ myeloid and CD34+/CD19+ lymphoid progenitors (n=8) is not affected by FTY720 treatment. Furthermore, pharmacologic doses of FTY720 markedly suppress leukemogenesis in SCID mice (n=13 per group) transplanted with myeloid and lymphoid progenitor cells transformed with p210BCR/ABL and p190BCR/ABL, respectively. In fact, the median survival has not yet been reached in FTY720-treated (10 mg/kg/day) BCR/ABL+ cell-injected mice. Conversely, all of untreated 32D-p210BCR/ABL, 32D-p210BCR/ABL(T315I) and BaF3-p190BCR/ABL leukemic mice died of an overt acute leukemia-like process with a median survival of 4.3, 4.8 and 4.1 weeks, respectively (P<0.001). After 11 weeks of FTY720 treatment, 80% and 90% of p210 and p190 mice, respectively, were alive and in molecular remission. Moreover, long-term (189 days) FTY720 daily administration (10 mg/kg/day) did not induce any adverse effect, and achieved sustained absence of BCR/ABL+ cells (assessed by nested RT-PCR) in 50% of mice transplanted with myeloid progenitors expressing the imatinib/dasatinib-resistant T315I p210BCR/ABL mutant. Mechanistically, the anti-leukemic effects of FTY720 are sphingosine 1-phosphate receptor 1 (SIP1)-mediated and dependent on the ability of FTY720 to activate PP2A phosphatase. That, in turn, inhibits the activity and expression of wild type and mutant p210 and p190 BCR/ABL oncoproteins and important regulators (e.g. Akt) of malignant cell survival and proliferation. Altogether, these results not only reinforce the importance of the PP2A tumor suppressor in the biology of Ph1 leukemias but, because FTY720 has been shown to be feasible in Phase I-III clinical trials for multiple sclerosis or solid organ transplant patients, they strongly support the use of this PP2A activator as a novel therapeutic approach for CML-BC and Ph1 ALL.

The Role of Wilms’ Tumor Protein 1 (WT1) in Chronic Myelogenous Leukemia Progression.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4344-4344
Author(s):  
Liliana R. Souza ◽  
Luiz Penalva ◽  
Morgan McLemore
Keyword(s):  
Cellular Proliferation ◽  
Wilms Tumor ◽  
Blast Crisis ◽  
Regulatory Gene ◽  
Critical Role ◽  
Myelogenous Leukemia ◽  
Hematopoietic Progenitors ◽  
Hematopoietic Stem ◽  
Over Expression ◽  
Exact Function

Abstract Wilms’ tumor protein 1 (WT1) is a key regulatory gene whose function is required for proper development and differentiation of the heart, retina, genito-urinary, olfactory and hematopoietic systems. WT1 over expression is a characteristic observed in blasts of Chronic Myeloid Leukemia (CML). Despite this apparent co-relation, a direct link between WT1 over expression and progression of CML to blast crisis has never been established. The two major isoforms of WT1 are generated by alternative splicing; an event that involves the use of two alternative splice sites at the end of exon 9. The outcome is the insertion or not of only 3 amino acids (lysine, threonine and serine; KTS) at the c-terminus of the protein. The ratio between these isoforms is conserved among tissues and disruption of this balance can end up causing developmental abnormalities. Our group is testing if the over expression of WT1 in hematopoietic precursors can lead to progression in a murine model of CML. Over expression of WT1 has been shown to block differentiation in myeloid cell lines. However, over expression of WT1 in primary hematopoietic cells has variable effects on differentiation and proliferation. These differences may reflect differences in vector design and/or assays to evaluate. We have utilized the Murine Stem Cell Vector (MSCV), a retroviral construct that has high efficiency of transducing murine hematopoietic stem cells, to generated retroviral constructs. The vector contains an internal ribosomal entry site allowing expression of WT1+KTS or WT1-KTS isoforms with and without Bcr-Abl/GFP, the causative protein in CML. Retroviral transduction of hematopoietic progenitors was performed for 48 hours and FACS sorted GFP+Sca+lin− cells were utilized for colony forming assays in methylcellulose and in liquid culture. Our results have shown that primary murine hematopoietic progenitors transduced with Bcr-Abl/GFP and WT1+KTS demonstrate dramatically greater cytokine independent growth than progenitors transduced with Bcr-Abl/GFP alone. In contrast, progenitors transduced with Bcr-Abl/GFP and WT1-KTS demonstrate impaired growth. Figure Figure In addition transduced cells will be used to rescue lethally irradiated mice what will provide an excellent model to determine if WT1 cooperates with BCR-ABL to induce blast crisis. The exact function of each WT1 isoform is still unknown. However, there is clear data that they have different properties and are involved in different functions. Several lines of evidence suggest a role for the +KTS isoform in splicing. During hematopoietic cell differentiation, levels of WT1 protein were determined to decrease drastically. This fluctuation in WT1 expression level may play a critical role in the process of differentiation. In conclusion, our results strongly suggest that WT1 expression influences Bcr-Abl induced growth with the isoforms WT1+KTS and WT1-KTS displaying differential effects. Our data indicate that +KTS enhances Bcr-Abl dependent cellular proliferation while -KTS isoform impairs proliferation.

Genetic Susceptibility to Therapy-Related Acute Murine Promyelocytic Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 14-14
Author(s):  
Ryan K. Funk ◽  
Taylor Maxwell ◽  
Masayo Izumi ◽  
Deepa Edwin ◽  
Friederike Kreisel ◽  
...  
Keyword(s):  
Median Survival ◽  
Qtl Analysis ◽  
Myeloid Leukemia ◽  
Single Copy ◽  
Promyelocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Chromosome 1 ◽  
Mouse Strains ◽  
Spleen Weight ◽  
Trait Locus

Abstract Therapy-related acute myelogenous leukemia (t-AML) is an important late adverse effect of alkylator chemotherapy. Susceptibility to t-AML has a genetic component, yet the specific genes and genetic variations that influence susceptibility are poorly understood. Our lab previously identified mouse strains that are susceptible (SWR/J) or resistant (C57BL/6J and C3H/HeJ) to t-AML induced by the alkylator, ethyl-N-nitrosourea (ENU). To study the genetic basis of these differences, we performed an F2 intercross between susceptible and resistant strains. A single copy of the hCG-PML-RARa (PR) transgene was bred into each mouse. PR is an initiating factor for acute promyelocytic leukemia, but requires cooperating mutations for full leukemic transformation. This provides a platform to detect gene X transgene (PR) and gene X environment (ENU) interactions that promote leukemogenesis. F2 mice were treated (n=141) or untreated (n=141) with ENU and sacrificed and analyzed when moribund. We also analyzed untreated PR+ (n=24) mice from the resistant C57BL/6J X C3H/HeJ (B6C3F1) background. Untreated B6C3F1 PR+ mice developed lethal myeloid leukemia (characterized by splenomegaly > 0.25g, WBC > 30 K/uL, and increased immature myeloid precursors in PB, BM, and spleen) with an incidence of 12.5% and a latency of 234 days. By contrast, 79.4% of untreated PR+ F2 mice developed myeloid leukemia with a latency of 108 days and median survival of 238 days. The earlier onset and increased incidence of leukemia in F2 mice confirm that SWR/J alleles confer increased susceptibility to AML. ENU treatment further increased the leukemia incidence (90.4% vs. 79.4%, p<0.0001 by logrank) and shortened the median survival (168 vs. 238 days) of PR+ F2 mice. F2 mice were genotyped using 357 informative SNPs across the genome to facilitate quantitative trait locus (QTL) mapping. QTL analysis was performed using leukemia-free survival, spleen weight, and WBC as quantitative traits. Because extramedullary hematopoeisis and increased WBC are markers of poor prognosis in human AML, we reasoned that identification of modifier alleles for these traits might also have potential clinical relevance. QTL analysis revealed five peaks associated with survival, 5 with spleen weight, and 3 with WBC. The 1 LPR (likelihood probability ratio) confidence intervals for the QTL range in size from 10 to 50 Mbp. Each region contains between 100 and 750 genes. The most significant peak (LPR=3.94) is a survival QTL on chromosome 1 from 93.4 to 120.5 Mbp that retains significance at the genome wide level. The QTL effect is large in ENU-treated animals but not discernible in untreated animals. Both the additive effect (−0.51, SE=0.17) and the dominant effect (0.62, SE=0.20) are significant at p<0.05. Genes with potential connections to leukemogenesis within this region include a serpin cluster, genes involved in apoptosis (Bcl2, Bok, Pdcd1 Phlpp), and cell cycle genes (Sept2 and Clasp1). Ongoing studies are focused on candidate gene evaluation and fine-mapping the QTL regions to identify the QTL genes and their variants. Validation of these genes in therapy-related leukemogenesis should provide a better understanding of t-AML susceptibility and lead to strategies that moderate t-AML risk in susceptible individuals.

scholarly journals Spontaneous chronic subdural hematoma development in chronic myeloid leukemia cases at remission phase under maintenance therapy, management strategy - a series with literature review

2016 ◽  
Vol 30 (3) ◽  
pp. 451-460
Author(s):  
Amol Raheja ◽  
Guru Dutta Satyarthee
Keyword(s):  
Subdural Hematoma ◽  
Myeloid Leukemia ◽  
Surgical Intervention ◽  
Haematological Malignancy ◽  
Blast Crisis ◽  
Chronic Subdural Hematoma ◽  
Myelogenous Leukemia ◽  
Temporal Region ◽  
Current Article ◽  
Remission Phase

AbstractChronic subdural hematoma (CSDH) is common squeal of trauma and rarely associated with anticoagulant therapy, antiplatelet, chemotherapeutic drugs, arteriovenous malformation, aneurysms and post-craniotomy. However its occurrence is very unusual with systemic haematological malignancy and mostly reported with acute myeloid leukemia; however incidence of SDH occurrence in chronic myelogenous leukemia (CML) is very rare. CML is a haematological malignancy characterized by chromosomal alteration, pathologically represents increased proliferation of the granulocytic cell line without loss of capacity to differentiate. CML has three phases - remission phase, accelerated phase and blast crisis. About 85 % of patients present in remission phase of disease and carries a favorable prognosis. As intracranial, subdural hematoma usually occur in the accelerated phase or blast crisis phase or extremely uncommon during chronic remission phase, although only those affected, who are neglecting therapeutic medication or discontinued therapy or rarely as an adverse effect of medications. However, important role of neurosurgeon lies in early detection and correction of platelet count and associated hematological abnormality as quite sizeable proportion of cases may not need surgical intervention instead can be managed conservatively under regular supervision in association with oncologist colleague, but few cases may need urgent surgical intervention. So, selecting a subgroup of CML cases in the remission phase requiring surgical intervention, presenting with CSDH is not only challenging, as failure to make an informed and timely precise decision can lead to catastrophic worse outcome and even mortality. So, purpose of current article is to formulate the management therapeutic plan. Authors report three cases of CML in chronic remission phase, receiving treatment under guidance of Haemto-oncologist at our institute presented with spontaneous chronic SDH. The mean age was 36 years (range 29- 44 years), 66% were male, headache was presenting feature in all 100% (n=3), 66% cases were hemiplegic and 33% unconscious each, in 66% cases CSDH were located on right fronto-temporal region and 33% had small left sided thin CSDH. About were 66% cases (n=2) were managed surgically by burr hole placement and drainage drain placement while 33% case (n=1), who had thin CSDH was managed conservatively.Favorable outcome was observed in 100% cases (n=3) Outcome was favorable in all of our cases.

scholarly journals Vitamin E in Chronic Myeloid Leukemia (CML) Prevention

2021 ◽  
Author(s):  
Lyudmyla Shvachko ◽  
Michael Zavelevich ◽  
Daniil Gluzman ◽  
Gennadii Telegeev
Keyword(s):  
Alkaline Phosphatase ◽  
Vitamin E ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Blast Crisis ◽  
K562 Cells ◽  
Leukemic Cells ◽  
Blast Cells ◽  
Differentiation Block

The resistance to inhibitors of tyrosine kinase necessitates novel approaches to the therapy of chronic myeloid leukemia (CML). The progression of CML to blast crisis is associated with down-regulation of C/EBP-alpha being involved in the differentiation block in leukemic blast cells. Moreover, lowered C/EBP-alpha expression correlates with resistance to imatinib in CML. We have demonstrated that vitamin E up-regulates expression of C/EBP-alpha and down-regulates expression of Snail transcription factor in K562 cells in vitro contributing to the putative recovery of myeloid differentiation potential. In parallel with increased CEBP alpha expression, Vitamin E treatment results in the decreasing expression of placental-like alkaline phosphatase and increasing expression of tissue non-specific alkaline phosphatase. We suggest that vitamin E could be used as the plausible biological modulator to prevent the progression to blast crisis and to overcome drug resistance of leukemic cells in CML.

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