Posted by rob on May 20, 2010 under Uncategorized | 
In this study, the possible prognostic value of this phenomenon was evaluated. Thirty-six Ph-positive CML patients were included in the study. In six patients, ACAs persisted after the disappearance of the Ph. A complete cytogenetic response (CCR) was obtained in five of these six patients, and five of six also had a high Sokal score. In all the other cases, ACAs disappeared together (in cases of response to therapy with imatinib) or persisted with the Ph (in cases of no response to imatinib). In the former cases, the primary origin of the Ph was demonstrated. CCR was obtained in 22 cases (17 with low to intermediate Sokal scores), while no response was observed in 8 patients (5 with a high Sokal score). Sokal score seems to maintain its prognostic value for patients in whom the Ph occurs …
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Authors: Puissant A, Auberger P
Resveratrol (RSV) is an attractive candidate for cancer therapy because of its ability to intervene at different levels in the AMPK/mTOR pathway. Indeed, RSV is unique in its capacity to inhibit both mTOR and S6 kinase and to activate AMPK. Our recent data reveals that RSV triggered autophagic cell death (ACD) in Chronic Myelogenous Leukemia (CML) cells, via both AMPK activation and JNK-mediated p62/SQSTM1 expression. Here we discuss how Resveratrol can mediate ACD in CML cells and the possibility of utilizing the AMPK/mTOR and JNK/p62 pathways via Resveratrol to combat CML and other hematopoietic malignancies.
PMID: 20458181 [PubMed - as supplied by publisher] (Source: Autophagy)
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A 40-year-old otherwise healthy man was diagnosed with chronic myelogenous leukemia (CML) in the first chronic phase 6 months ago after a routine annual examination. He took imatinib mesylate for 3 months but experienced intolerable side effects that resolved with discontinuation of the drug. He is about to undergo a myeloablative transplant from his HLA-matched brother. (Source: Biology of Blood and Marrow Transplantation)
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(Source: Journal of Biological Chemistry)
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(Source: Journal of Biological Chemistry)
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Authors: Lippert E, Etienne G, Mozziconacci MJ, Laibe S, Gervais C, Girault S, Gachard N, Tigaud I, Dastugue N, Huguet F, Fort MP, Legros L, Eclache V, Mahon FX
In chronic myelogenous leukemia (CML) cytogenetic abnormalities found in addition to the t(9;22) translocation may impact the response to therapy. Loss of the Y chromosome is generally overlooked in this context, owing to its relatively frequent occurrence in healthy elderly patients. In this multicenter retrospective study, the outcome after imatinib treatment of 30 CML patients with karyotype showing Y chromosome loss (Y-) was compared to 30 Y+ control males diagnosed and treated at the same time, in the same institutions. Y- patients had significantly delayed cytogenetic and molecular responses, lower event-free survival and…
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No abstract. (Source: American Journal of Hematology)
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Abstract BS69 was originally identified as an adenovirus E1A-binding protein and was found to be involved in multiple cellular events.
A recent array-based study implicated the presence of copy number variations (CNVs) of BS69 in the genomes of acute myelogenous
leukemia. CNVs are present in the general population at varying degrees and have been found to associate with various types
of diseases including hematological malignancies. However, most of the current studies focused on the genome-wide screening
of CNVs, and the functional impact of such regions needs to be extensively investigated in large amount of clinical samples.
Thus, in our study, we collected 617 bone marrow samples from multi-types of hematological malignancies as well as healthy
controls. We found signi…
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In this study, the biological activity of
16 LCRCs to a chronic myelogenous leukemia cell line, K562, was evaluated. As a result, two compounds, 2-(4-butoxyphenyl)-5-(4-hydroxyphenyl)pyrimidine
(compound 7) and 2-{4-(4-hexyloxyphenyl)phenyl}-5-hydroxypyrimidine (compound 9) showed marked growth suppression of K562
cells at ?M range. These compounds are similar in structure with a core of three aromatic rings including a pyrimidine ring
and residues of one alkyl chain and one hydroxide on either side. In addition, only compound 7 induced the activation of p38
mitogen-activated protein kinase and c-Jun N-terminal kinase, and apoptosis of K562 cells. The contrasting results between
compounds 7 and 9 indicate different mechanisms to suppress the cell proliferation between the two compou…
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Posted by rob on under Uncategorized |
In this study, the biological activity of 16 LCRCs to a chronic myelogenous leukemia cell line, K562, was evaluated. As a result, two compounds, 2-(4-butoxyphenyl)-5-(4-hydroxyphenyl)pyrimidine (compound 7) and 2-{4-(4-hexyloxyphenyl)phenyl}-5-hydroxypyrimidine (compound 9) showed marked growth suppression of K562 cells at muM range. These compounds are similar in structure with a core of three aromatic rings including a pyrimidine ring and residues of one alkyl chain and one hydroxide on either side. In addition, only compound 7 induced the activation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase, and apoptosis of K562 cells. The contrasting results between compounds 7 and 9 indicate different mechanisms to suppress the cell proliferation between the two compounds. T…
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Abstract: Imatinib mesylate is used with increasing frequency and duration for the treatment of chronic myelogenous leukemia (CML), gastrointestinal stromal tumor (GIST), and other neoplastic conditions. Although muscular complaints are common, elevations of creatine kinase (CK) are listed as (Source: Leukemia Research)
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In this study, we found
that the CD34+ subpopulation in the CML cell line K562 had a higher expression of SOD1 than that in the CD34 negative cells.
Knockdown of SOD1 in CD34+ cells had no significant effects on cell survival and growth, while it sensitized the CD34+ cells
to imatinib therapy. N-acetyl-L cysteine (NAC) blocked the pro-apoptotic effects of SOD1 knockdown, suggesting the antioxidant
effects of SOD1 was essential for the resistance of CD34+ cells to imatinib therapy. In summary, our results suggest that
antagonizing the enhanced endogenous antioxidant activity in leukemia stem cells sheds lights on CML therapy.
Content Type Journal ArticleCategory Original PaperDOI 10.1007/s12032-010-9529-9Authors
Li Liu, Fourth Military Medical University Department of Hematology…
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Authors: Crespan E, Radi M, Zanoli S, Schenone S, Botta M, Maga G
The tyrosine kinase Src and its close homolog Abl, both play important roles in chronic myelogenous leukemia (CML) progression and Imatinib resistance. No clinically approved inhibitors of the drug-resistant AblT315I exist to date. Here, we present a thorough kinetic analysis of two potent dual Src-Abl inhibitors towards wild type Src and Abl, and the AblT315I mutant. Our results show that the most potent compound BO1 shows only a modest loss of potency (fourfold) towards the AblT315I mutant in vitro and was an ATP-competitive inhibitor of wild type Abl but it acted as a non-competitive inhibitor in the case of AblT315I.
PMID: 20451394 [PubMed - as supplied by publisher] (Source: Bioorganic and Medicinal Chemistry)
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Targeted therapies have made their way into clinical practice during the past decade. They have caused a major impact on the survival of cancer patients in many areas of clinical oncology and hematology. Indeed, in some hematologic malignancies, such as chronic myelogenous leukemia or non-Hodgkin’s lymphomas, biologicals and antibodies specifically designed to target tumour-specific proteins have revolutionized treatment standards. In solid tumours, new drugs targeting EGF- or VEGF- receptors are now approved and are entering clinical practise for treatment of colon, lung, kidney and other cancers, either alone or in combination with conventional treatment approaches.Recent data have now shown that molecular targeted therapy might display efficacy in patients with head and neck squamous ce…
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Conclusion
With these similar outcomes observed in older patients, we conclude that older age alone should not be considered a contraindication to HCT. (Source: Journal of Clinical Oncology)
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Hairy enhancer of split 1 (Hes1) is a basic helix-loop-helix transcriptional repressor that affects differentiation and often helps maintain cells in an immature state in various tissues. Here we show that retroviral expression of Hes1 immortalizes common myeloid progenitors (CMPs) and granulocyte-macrophage progenitors (GMPs) in the presence of interleukin-3, conferring permanent replating capability on these cells. Whereas these cells did not develop myeloproliferative neoplasms when intravenously administered to irradiated mice, the combination of Hes1 and BCR-ABL in CMPs and GMPs caused acute leukemia resembling blast crisis of chronic myelogenous leukemia (CML), resulting in rapid death of the recipient mice. On the other hand, BCR-ABL alone caused CML-like disease when expressed in c…
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Authors: A Puissant, M Dufies, S Raynaud, J-P Cassuto
& P Auberger (Source: Leukemia)
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Authors: Li W, Hongli Z, Xuedong S, Tieqiang L, Mei G, Guangxian L, Qiyun S, Jianhui Q, Danhong W, Changlin Y, Kaixun H, Zheng D, Huisheng A
Clinical studies have shown that NST has better therapeutic results with chronic myelogenous leukemia (CML) than acute leukemia (AL), but whether the generation of graft-versus-leukemia (GVL) effects is different between AL and CML patients early after NST has not yet been studied, so we used a pentamer-staining technique in combination with ICCS to detect WT1(+)CD8(+)CTL/WT1(+)Tc1 and WT1(+)Th1 cells in these two groups of patients. Results showed that the emergence time of WT1(+)CD(8) (+)CTL/WT1(+)Tc1 cells after NST in AL patients was similar to that in CML patients (P = 0.58), while the emergence time of WT1(+)Th1 cells after NST in AL patient…
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Authors: Nair RR, Tolentino J, Hazlehurst LA
Bcr-abl kinase inhibitors have provided proof of principal that targeted therapy holds great promise for the treatment of cancer. However, despite the success of these agents in treating chronic myelogenous leukemia (CML), the majority of patients continue to present with minimal residual disease contained within the bone marrow microenvironment. These clinical observations suggest that the bone marrow microenvironment may provide survival signals that contribute to the failure to eliminate minimal residual disease. The bone marrow microenvironment is comprised of multiple sub-domains which vary in cellular composition and gradients of soluble factors and matrix composition. Experimental evidence indicates that exposure of tumor cells to eit…
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Imatinib 400 mg daily is the standard treatment for patients with chronic myelogenous leukemia (CML). The safety and efficacy of imatinib in CML patients with pre-existing liver and/or renal dysfunction has not been analyzed.The authors analyzed the outcome of 259 patients with early chronic phase CML treated with imatinib (starting dose 400 mg in 50, 800 mg in 209). Pre-existing liver and/or renal dysfunction was seen in 38 (15%) and 11 (4%) patients, respectively.Dose reductions were required in 91 (43%) of 210 patients with normal organ function, compared with 8 (73%) of 11 (P = .065) with renal dysfunction, and 19 (50%) of 38 (P = .271) with liver dysfunction. Grade 3-4 hematologic toxicities including anemia (29%, 10%, and 7% of patients with renal dysfunction, liver dysfunction, and …
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