Posted by rob on September 30, 2010 under Uncategorized | 
Activation-induced cytidine deaminase (AID) is required for somatic hypermutation and immunoglobulin (Ig) class switch recombination in germinal center (GC) B cells. Occasionally, AID can target non-Ig genes and thereby promote GC B-cell lymphomagenesis. We recently showed that the oncogenic BCR-ABL1 kinase induces aberrant expression of AID in pre-B acute lymphoblastic leukemia (ALL) and lymphoid chronic myelogenous leukemia blast crisis. To elucidate the biological significance of aberrant AID expression, we studied loss of AID function in a murine model of BCR-ABL1 ALL. Mice transplanted with BCR-ABL1–transduced AID–/– bone marrow had prolonged survival compared with mice transplanted with leukemia cells generated from AID+/+ bone marrow. Consistent with a causative ro…
More
Posted by rob on under Uncategorized |
Abstract: The age role was evaluated in 117 consecutive patients with newly diagnosed CML at our Institution treated with front-line Imatinib from 9/02 to 3/08. Forty patients (34.1%) aged ?65 years and 77 (65.9%) (Source: Leukemia Research)
More
Posted by rob on under Uncategorized |
Often, resistance to drugs is an obstacle to a successful treatment of cancer. In spite of the importance of the problem, the actual mechanisms that control the evolution of drug resistance are not fully understood. Many attempts to study drug resistance have been made in the mathematical modeling literature. Clearly, in order to understand drug resistance, it is imperative to have a good model of the underlying dynamics of cancer cells. One of the main ingredients that has been recently introduced into the rapidly growing pool of mathematical cancer models is stem cells. Surprisingly, this all-so-important subset of cells has not been fully integrated into existing mathematical models of drug resistance. In this work we incorporate the various possible ways in which a stem cell may divide…
More
Posted by rob on September 29, 2010 under Uncategorized |
Long-term exposure of leukemia cells to multi-targeted tyrosine kinase inhibitor induces activations of AKT, ERK and STAT5 signaling via epigenetic silencing of the PTEN gene.
Leukemia. 2010 Sep;24(9):1631-40
Authors: Nishioka C, Ikezoe T, Yang J, Yokoyama A
Imatinib induces complete molecular response in patients with chronic myeloid leukemia (CML) and chronic eosinophilic leukemia (CEL). However, development of resistance to imatinib has emerged as an important clinical problem for molecular-targeted therapy in CML and CEL. In this study, we have established the imatinib-resistant CEL EOL-1 sub-lines (designated as EOL-1R) by culturing cells with increasing concentrations of imatinib for 6 months. Interestingly, EOL-1R cells showed epigenetic silencing of the phosphatase and tensin homolog deleted on chromosome ten (PTEN) gene. Exposure of EOL-1R cells to imatinib failed to dephosphorylate AKT, ERK and STAT5, although PDGFRalpha was effectively inactivated. The forced expression of PTEN negatively regulated these signal pathways and sensitized EOL-1R cells to imatinib. Notably, hypermethylation of the promoter region of the PTEN gene in association with the downregulation of this gene’s transcripts was identified in imatinib-resistant leukemia cells isolated from individuals with CEL, CML and Philadelphia-positive acute lymphoblastic leukemia. In addition, anti-epigenetic agents restored PTEN expression, resulting in the sensitization of EOL-1R cells to imatinib. Taken together, epigenetic silence of PTEN is one of the mechanisms that cause drug resistance in individuals with leukemia after exposure to imatinib. Anti-epigenetic agents may be useful for overcoming drug resistance in such a case.
PMID: 20596030 [PubMed - indexed for MEDLINE]
More
Posted by rob on under Uncategorized |
Critical molecular pathways in cancer stem cells of chronic myeloid leukemia.
Leukemia. 2010 Sep;24(9):1545-54
Authors: Chen Y, Peng C, Sullivan C, Li D, Li S
Inhibition of BCR-ABL with kinase inhibitors in the treatment of Philadelphia-positive (Ph(+)) chronic myeloid leukemia (CML) is highly effective in controlling but not curing the disease. This is largely due to the inability of these kinase inhibitors to kill leukemia stem cells (LSCs) responsible for disease relapse. This stem cell resistance is not associated with the BCR-ABL kinase domain mutations resistant to kinase inhibitors. Development of curative therapies for CML requires the identification of crucial molecular pathways responsible for the survival and self-renewal of LSCs. In this review, we will discuss our current understanding of these crucial molecular pathways in LSCs and the available therapeutic strategies for targeting these stem cells in CML.
PMID: 20574455 [PubMed - indexed for MEDLINE]
More
Posted by rob on under Uncategorized |
Inhibition of class II phosphoinositide 3-kinase gamma expression by p185(Bcr-Abl) contributes to impaired chemotaxis and aberrant homing of leukemic cells.
Leuk Lymphoma. 2010 Jun;51(6):1098-107
Authors: Yu W, Sun X, Tang H, Tao Y, Dai Z
The expression of p185(Bcr-Abl) in Ba/F3 cells inhibits the chemotactic response of these cells to SDF1alpha. A mutant p185(Bcr-Abl) with deletion of amino acids from 176 to 426 (p185(Delta176-426)) is deficient in suppressing SDF1alpha-stimulated chemotaxis. Comparison of the gene expression profiles among parental Ba/F3 cells and cells transformed by p185(Bcr-Abl) and p185(Delta176-426) reveals that class II phosphoinositide 3-kinase gamma (PI3KC2gamma) expression is markedly down-regulated by p185(Bcr-Abl) but not p185(Delta176-426). Furthermore, knockdown of PI3KC2gamma expression in p185(Delta176-426) cells is sufficient to suppress SDF1alpha-stimulated chemotaxis and to promote infiltration of these cells into the liver. Together, these studies suggest that inhibition of PI3KC2gamma expression may represent a mechanism by which Bcr-Abl suppresses SDF1alpha-induced chemotaxis and induces abnormal homing of leukemic cells.
PMID: 20536348 [PubMed - indexed for MEDLINE]
More
Posted by rob on under Uncategorized |
Molecular pathways to CML stem cells.
Int J Hematol. 2010 Jun;91(5):748-52
Authors: Rice KN, Jamieson CH
Imatinib has revolutionized the treatment of chronic myeloid leukemia (CML), but it does not cure the disease. Many patients never achieve significant cytogenetic or molecular responses. Some develop resistance to the drug, while others are simply unable to tolerate it. Unfortunately, most will relapse if the drug is discontinued. This is particularly true in patients with advanced disease, who tend to develop resistance rapidly and are unlikely to achieve durable remission with single-agent tyrosine kinase inhibitor therapy. A growing body of evidence suggests that the reason imatinib does not cure CML is that it is unable to eradicate the leukemic stem cells (LSC). LSC are a tiny population of cancer cells with the capacity to recapitulate the disease. These quiescent cells have subverted properties of normal hematopoietic stem cells, allowing them to avoid apoptosis, evade innate immunity, renew themselves, and survive long term. Here, we review the studies that have identified the deregulated molecular pathways responsible for the generation of CML stem cells and discuss implications for therapy.
PMID: 20533007 [PubMed - indexed for MEDLINE]
More
Posted by rob on under Uncategorized |
Imatinib dose escalation in two patients with chronic myeloid leukemia, with low trough imatinib plasma levels measured at various intervals from the beginning of therapy and with suboptimal treatment response, leads to the achievement of higher plasma levels and major molecular response.
Int J Hematol. 2010 Jun;91(5):897-902
Authors: Faber E, Friedecký D, Micová K, Divoká M, Katrincsáková B, Rozmanová S, Jarosová M, Indrák K, Adam T
Despite the prognostic value of trough imatinib plasma levels (IPL) identified in some studies, no recommendations for the use of IPL results in routine management of CML patients have been issued. We report two patients in whom daily imatinib dose was increased from 400 to 600 or 800 mg because of low IPL found at various intervals from the beginning of treatment (7 measurements; mean IPL values = 616.33 and 764.5 ng/mL, respectively). Both patients achieved suboptimal response according to the European LeukemiaNet criteria (complete cytogenetic response was not achieved after 1 year of treatment in patient 1 and major molecular response after 47 months of standard-dose imatinib therapy in patient 2). In addition, we have demonstrated low hOCT-1 expression at diagnosis in both patients, retrospectively. Escalation of imatinib daily dose resulted in a significant increase of IPL (6 measurements; mean = 1790 and 1416.66 ng/mL, respectively) and in the achievement of complete cytogenetic response in patient 1 after 3 months and major molecular response within 15 and 6 months in both patients. Our cases demonstrate that low IPL identified at various non-predefined intervals from the beginning of therapy may be used for deciding on dose escalation in selected CML patients in the routine clinical setting, especially in cases with suboptimal treatment response.
PMID: 20437122 [PubMed - indexed for MEDLINE]
More
Posted by rob on under Uncategorized |
High frequency of MEFV gene mutations in patients with myeloid neoplasm.
Int J Hematol. 2010 Jun;91(5):758-61
Authors: Oktenli C, Sayan O, Celik S, Erikci AA, Tunca Y, Terekeci HM, Umur EE, Sanisoglu YS, Torun D, Tangi F, Sahan B, Nalbant S
We aimed to investigate the rate of MEFV, the gene mutated in familial Mediterranean fever, mutations in patients with myeloid neoplasm and to determine if known mutations of MEFV cause a tendency for myeloid neoplasms. The frequency of the five most common MEFV gene mutations (M694V, M680I, V726A, E148Q and M694I) was determined in 26 patients with myeloid neoplasm. We identified 1 homozygous (E148Q/E148Q), 1 compound heterozygous (M694V/E148Q) and 5 heterozygous MEFV gene mutations; none had their own and/or family history compatible with familial Mediterranean fever. The mean overall mutation rate was 0.269. We found a high frequency of carriers in patients with myelodysplastic syndrome (66.6%), polycythemia vera (33.3%) and acute myeloid leukemia (28.6%). However, there was no MEFV gene mutation in patients with chronic myeloid leukemia. In conclusion, this study reports for the first time a possibly high prevalence of MEFV gene mutations in patients with myeloid neoplasm, especially myelodysplastic syndrome, polycythemia vera and acute myeloid leukemia. Our findings could open new perspectives for MEFV gene mutations in myeloid neoplasms and its association with tumor promotion. Further research is needed to determine the actual role of MEFV gene mutations in these malignancies.
PMID: 20437121 [PubMed - indexed for MEDLINE]
More
Posted by rob on under Uncategorized |
Clinical features of dasatinib-induced large granular lymphocytosis and pleural effusion.
Int J Hematol. 2010 Jun;91(5):799-807
Authors: Nagata Y, Ohashi K, Fukuda S, Kamata N, Akiyama H, Sakamaki H
During follow-up of leukocyte counts in 20 consecutive patients (age range 29-81 years) treated with dasatinib, 9 patients (7 chronic myeloid leukemia in chronic phase, 2 Philadelphia chromosome-positive acute lymphoid leukemia in complete remission) developed lymphocytosis (>3,000/microl). Peripheral blood smears revealed a population of large granular lymphocytes. Large granular lymphocytosis (LGL) was first noted between 1 and 8 months after initiation of dasatinib, and it has persisted up to 33 months from the onset of LGL in one patient. Peak numbers of large granular lymphocytes ranged from 2,915 to 17,425/microl. The occurrence of LGL might interfere with achieving molecular response (MR, real-time quantification of major BCR-ABL1 mRNA less than 50 copies/microg RNA) in our small cohort; 8 (89%) of 9 patients with LGL attained MR, while only 6 (55%) of 11 patients without LGL eventually achieved MR. With respect to the relationship between LGL and pleural effusion (PE), 3 (27%) of 11 patients without LGL developed PE, while 5 (56%) of 9 patients with LGL developed PE. Moreover, the mean peak number of LGL was 9,215/microl, which was much higher than the mean peak number (4,635/microl) of LGL in patients without PE. These results may suggest possible association of both events in our cohorts.
PMID: 20405252 [PubMed - indexed for MEDLINE]
More
Posted by rob on under Uncategorized |
Mutations in ABL kinase domain are associated with inferior progression-free survival.
Leuk Lymphoma. 2010 Jun;51(6):1072-8
Authors: Sharma P, Mohanty S, Kochupillai V, Kumar L
Imatinib mesylate is currently the drug of choice for all phases of chronic myeloid leukemia (CML). Despite the initial high rates of hematological and cytogenetic responses, many patients develop resistance. We prospectively studied 40 patients with CML with primary cytogenetic resistance to imatinib mesylate. A semi-nested reverse transcriptase-PCR approach was used for amplification of the ABL kinase domain, which was then subjected to direct sequencing for the detection of point mutations. Expression of BCR-ABL transcripts was quantified using the real-time Taqman assay, and BCR-ABL gene amplification was detected using fluorescence in situ hybridization. Twelve different point mutations were detected in 18/40 (45%) patients. Five patients had mutations in the P-loop region and 13 had mutations in other regions of the BCR-ABL kinase domain. Progression-free survival at 2 years was inferior for patients with mutations compared to those without mutations (72% vs. 95%, p < 0.0045). The BCR-ABL fusion gene was over-expressed in five patients (5/18); the mean BCR-ABL/ABL ratio was 75.38 vs. 28.72 for imatinib responders, p < 0.001. Amplification of the BCR-ABL fusion gene was detected in 4/40 (10%) patients. Point mutation was the major mechanism of primary cytogenetic resistance to imatinib mesylate in the present study. Patients with mutations had inferior progression-free survival compared to those without mutations. Regular monitoring for the presence of point mutations in the ABL kinase region may identify such patients early, with an opportunity to intervene.
PMID: 20367437 [PubMed - indexed for MEDLINE]
More
Posted by rob on under Uncategorized |
Bortezomib decreases Rb phosphorylation and induces caspase-dependent apoptosis in Imatinib-sensitive and -resistant Bcr-Abl1-expressing cells.
Oncogene. 2010 Jun 3;29(22):3276-86
Authors: Albero MP, Vaquer JM, Andreu EJ, Villanueva JJ, Franch L, Ivorra C, Poch E, Agirre X, Prosper F, Pérez-Roger I
The use of c-abl-specific inhibitors such as Imatinib (IM) or Dasatinib has revolutionized the treatment of chronic myeloid leukemia (CML). However, a significant percentage of patients become resistant to IM. In this report, we have analyzed the possibility of using the proteasome as a molecular target in CML. Our results show that cells that express Bcr-Abl1 are more sensitive to the inhibition of the proteasome with Bortezomib (Btz) than control cells. This treatment reduces the proliferation of Bcr-Abl1-expressing cells, by inactivating NF-kappaB2 and decreasing the phosphorylation of Rb, eventually leading to an increase in caspase-dependent apoptosis. Furthermore, we show that Btz also induces cell-cycle arrest and apoptosis in cells expressing Bcr-Abl1 mutants that are resistant to IM. These results unravel a new molecular target of Btz, that is the Rb pathway, and open new possibilities in the treatment of CML especially for patients that become resistant to IM because of the presence of the T315I mutation.
PMID: 20305692 [PubMed - indexed for MEDLINE]
More
Posted by rob on under Uncategorized |
Glyoxalase-I is a novel target against Bcr-Abl+ leukemic cells acquiring stem-like characteristics in a hypoxic environment.
Cell Death Differ. 2010 Jul;17(7):1211-20
Authors: Takeuchi M, Kimura S, Kuroda J, Ashihara E, Kawatani M, Osada H, Umezawa K, Yasui E, Imoto M, Tsuruo T, Yokota A, Tanaka R, Nagao R, Nakahata T, Fujiyama Y, Maekawa T
Abl tyrosine kinase inhibitors (TKIs) such as imatinib and dasatinib are ineffective against Bcr-Abl(+) leukemic stem cells. Thus, the identification of novel agents that are effective in eradicating quiescent Bcr-Abl(+) stem cells is needed to cure leukemias caused by Bcr-Abl(+) cells. Human Bcr-Abl(+) cells engrafted in the bone marrow of immunodeficient mice survive under severe hypoxia. We generated two hypoxia-adapted (HA)-Bcr-Abl(+) sublines by selection in long-term hypoxic cultures (1.0% O(2)). Interestingly, HA-Bcr-Abl(+) cells exhibited stem cell-like characteristics, including more cells in a dormant, increase of side population fraction, higher beta-catenin expression, resistance to Abl TKIs, and a higher transplantation efficiency. Compared with the respective parental cells, HA-Bcr-Abl(+) cells had higher levels of protein and higher enzyme activity of glyoxalase-I (Glo-I), an enzyme that detoxifies methylglyoxal, a cytotoxic by-product of glycolysis. In contrast to Abl TKIs, Glo-I inhibitors were much more effective in killing HA-Bcr-Abl(+) cells both in vitro and in vivo. These findings indicate that Glo-I is a novel molecular target for treatment of Bcr-Abl(+) leukemias, and, in particular, Abl TKI-resistant quiescent Bcr-Abl(+) leukemic cells that have acquired stem-like characteristics in the process of adapting to a hypoxic environment.
PMID: 20139893 [PubMed - indexed for MEDLINE]
More
Posted by rob on September 28, 2010 under Uncategorized |
Long-term outcomes of HLA-matched sibling compared with mismatched related and unrelated donor hematopoietic stem cell transplantation for chronic phase chronic myelogenous leukemia: a single institution experience in China.
Ann Hematol. 2010 Sep 25;
Authors: Liu QF, Xu XJ, Chen YK, Sun J, Zhang Y, Fan ZP, Xu D, Jiang QL, Wei YQ, Huang F, Feng R, Liu XL, Xu B, Meng FY
Allogeneic hematopoetic stem cell transplantation (allo-HSCT) remains the only curative therapy for chronic myelogenous leukemia (CML). In this study, the long-term outcomes of HLA-matched sibling donor (MSD) with mismatched related donor (MRD) and unrelated donor (URD) transplantation for CML in the first chronic phase (CML-CP1) using different graft vs. host disease (GVHD) prophylaxis regimens according to donor source and the degree of HLA matching were compared. The data of 91 patients with CML-CP1 were analyzed with respect to GVHD, overall survival (OS), and transplant-related mortality (TRM). The incidence of grade II-IV acute GVHD was 25.5% in the MSD and 40.5% in the MRD/URD group (Pâ??=â??0.133). The 1-year cumulative incidence of chronic GVHD was not different between the MSD and the MRD/URD groups, while extensive chronic GVHD was different between the two groups (31.9% vs. 10.8%, Pâ??=â??0.023). The 5-year cumulative relapse rate was not different between the MSD and the MRD/URD groups, while TRM was different between the two groups (6.6% vs. 26.3%, Pâ??=â??0.010). The 5-year cumulative OS was 90.9%, 71.5%, and 85.4% in the MSD, the MRD/URD, and the HLA allele-matched URD transplantation, respectively (MSD vs. MRD/URD, Pâ??=â??0.013; MSD vs. HLA allele-matched URD, Pâ??=â??0.437). In conclusion, survival in HLA allele-matched URD is equivalent to MSD, but in MRD and mismatched URD is inferior to MSD in patients with CML-CP1 undergoing allo-HSCT using different GVHD prophylaxis regimens according to donor source and degree of HLA matching. Patients undergoing MRD/URD transplantation have an equal quality of life as patients undergoing MSD transplantation.
PMID: 20872002 [PubMed - as supplied by publisher]
More
Posted by rob on under Uncategorized |
Is there a role for autologous stem cell transplantation for patients with acute myelogenous leukaemia? A retrospective analysis.
Biol Blood Marrow Transplant. 2010 Sep 23;
Authors: Novitzky N, Thomas V, du Toit C, McDonald A
INTRODUCTION: For patients with AML who are unable to secure an acceptable HLA donor, the role of autologous stem cell transplantation has remained controversial. Its effectiveness remains unclear as, when analysed on intention to treat strategies, a significant number do not undergo the procedure, while others seem to fail therapy from pre transplant recurrences. METHODS: To improve our counselling to our patients on these two therapeutic options, we compared the outcome of patients in first remission of AML who actually underwent autologous or allogeneic transplantation. The choice for the type of graft was based on availability of HLA identical siblings. Patients received myeloablative conditioning followed by allogeneic or autologous cytokine mobilised peripheral blood stem cell transplantation. For prophylaxis of graft vs. host disease, grafts were incubated ex vivo with anti CD52 antibodies and patients were prescribed cyclosporin until day 90. Patients were stratified by clinical and laboratory factors as well as cytogenetic risk. The end points were TRM, DFS and OS. RESULTS: The median presentation age for both transplant groups was 35 (14-60) years. Of the 112 consecutive patients achieving remission, autologous or allogeneic grafts were transplanted to 43 and 32 patients respectively. There was no significant difference in the presentation clinical features, laboratory parameters, marrow morphology or proportion of low and intermediate cytogenetic risk for both transplant options. Treatment mortality as well as relapse rate was similar (14 and 15%; 39 and 27%, respectively). At a median of 1609 and 1819 post transplant days 56% and 63% in each group survive. In univariate analysis performance status, cytogenetic risk, morphological features of dysplasia, blast count and LDH were significant factors for survival. While for the entire group there was no difference in survival between both modalities, all patients with unfavourable cytogenetics receiving an autologous graft died of disease recurrence (3 year survival 35% vs 0%; p= 0.05). CONCLUSIONS: We conclude that patients with AML who have low or intermediate cytogenetic risk undergoing myeloablative conditioning followed by autologous or allogeneic T-cell depleted stem cell transplantation appeared to have similar outcome. However, those with unfavourable karyotype are unlikely to be cured with autologous grafts and are candidates for experimental modalities.
PMID: 20870030 [PubMed - as supplied by publisher]
More
Posted by rob on September 27, 2010 under Uncategorized |
In conclusion, survival in HLA allele-matched URD is equivalent to MSD, but in MRD and mismatched URD is inferior
to MSD in patients with CML-CP1 undergoing allo-HSCT using different GVHD prophylaxis regimens according to donor source and
degree of HLA matching. Patients undergoing MRD/URD transplantation have an equal quality of life as patients undergoing MSD
transplantation.
Content Type Journal ArticleDOI 10.1007/s00277-010-1081-3Authors
Qi-fa Liu, Department Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515 ChinaXiao-jun Xu, Department Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515 ChinaYin-kui Chen, Department Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515 ChinaJing Sun, Department Hemato…
More
Posted by rob on September 25, 2010 under Uncategorized |
Combination of the histone deacetylase inhibitor valproic acid with oral hydroxyurea or 6-mercaptopurin can be safe and effective in patients with advanced acute myeloid leukaemia – a report of five cases.
Hematology. 2010 Oct;15(5):338-43
Authors: Fredly H, Stapnes Bjørnsen C, Gjertsen BT, Bruserud O
Disease-stabilizing therapy with the histone deacetylase inhibitor valproic acid and all-trans retinoic acid (ATRA) has been investigated in acute myelogenous leukemia (AML) in a number of trials. Experimental studies suggest that valproic acid induces a broad chemoresistant phenotype in human AML cells; however, clinical observations combining valproic acid with conventional therapy in a disease-stabilizing setting have not been reported that would confirm this as a clinical issue. We describe five patients receiving oral treatment with low-dose oral 6-mercaptopurin and/or hydroxyurea together with ATRA+valproric acid+theophylline. Hyperleukocytosis was controlled by low doses of the cytotoxic drugs, no unexpected toxicity appeared and the increases in normal peripheral blood cell counts induced by ATRA+valproic acid+theophylline were maintained during therapy. In two patients increasing blast counts later occurred during chemotherapy; a change to the alternative cytotoxic drug was then effective in controlling hyperleukocytosis. We conclude that valproic acid+ATRA+theophylline combined with 6-mercaptopurin or hydroxyurea can be safe and effective in palliative treatment of human AML.
PMID: 20863429 [PubMed - in process]
More
Posted by rob on under Uncategorized |
Decision Resources, one of the world’s leading research and advisory firms for pharmaceutical and healthcare issues, finds that growth in the leukemia market will be driven mostly by chronic myelogenous leukemia (CML) therapies (Novartis’s Gleevec and Tasigna and Bristol-Myers Squibb’s Sprycel) and chronic lymphocytic leukemia (CLL) therapies (Biogen Idec/Roche’s Rituxan and Cephalon’s Treanda) until 2015, when patent and orphan-drug exclusivities of key brands will impact the sustainability of this growth… (Source: Health News from Medical News Today)
More
Posted by rob on September 24, 2010 under Uncategorized |
The Effect of Imatinib Mesylate for Newly Diagnosed Philadelphia Chromosome-Positive, Chronic-Phase Myeloid Leukemia in Sub-Saharan African Patients: The Experience of Côte d’Ivoire.
Adv Hematol. 2010;2010:
Authors: Koffi KG, Nanho DC, N’dathz E, Kouehion P, Dissieka R, Attia A, Mozard K, Tolo A, Boidy K, Meité N, Ayemou R, Sekongo M, Tea N, Sanogo I
Imatinib mesylate, showed encouraging activity in chronic myelogenous leukemia. However, there are few data regarding his efficacy and response monitoring in Sub-Saharan African patients. Our objective was to assess response to imatinib mesylate (Glivec) in Côte d’Ivoire patients with newly diagnosed Chronic Myeloid Leukemia (CML). From May 2005 to September 2009, we treated 42 patients (40 years; range 16-69) with Philadelphia chromosome (Ph+) positive in chronic phase CML with oral imatinib mesylate at daily doses of 400 mg. Overall survival (OS) and frequency of complete or major cytogenetic remission (CCR/MCR) were evaluated. At a median follow up of 32 (range 7.6-113) months, the CHR rate in our study group was 76%. A major CR was found in 19 patients (45%) with 17% and 29% complete and partial CR respectively. There were no significant differences in the incidence of major cytogenetic response by known prognostics factors. Median time to CHR was 8 months (range 0.4-25), and 16 months (range: 0.1-36) for CR. Projected 5-year OS rate was 72% (95%CI 42-88). We conclude that imatinib therapy sub-Saharan African CML patients is very promising and has favorably changed the prognosis for black African patients with CML.
PMID: 20862197 [PubMed - in process]
More
Posted by rob on under Uncategorized |
Myelodysplastic Syndromes–Many New Drugs, Little Therapeutic Progress.
Mayo Clin Proc. 2010 Sep 22;
Authors: Tefferi A
Myelodysplastic syndromes (MDS) constitute a form of blood cancer that primarily affects the elderly and is characterized by anemia (or other cytopenias) and a high risk of leukemic transformation. The World Health Organization (WHO) system has formally classified MDS as 1 of 5 myeloid malignancies that also include acute myeloid leukemia (AML) and myeloproliferative neoplasms. All myeloid malignancies, including MDS, are clonal stem cell diseases. Unlike the case with BCR-ABL1-positive chronic myelogenous leukemia, the disease-causing mutation in MDS is currently unknown. It is generally believed that the MDS phenotype is additionally affected by secondary mutations, genetic haploinsufficiency, epigenetic changes, and altered host response that result in cytokine, immune, and bone marrow stromal changes. Unfortunately, none of this information has successfully been translated into a robust pathogenetic framework or effective targeted therapy.
PMID: 20861462 [PubMed - as supplied by publisher]
More
