Posted by rob on May 31, 2009 under Uncategorized | 
Authors: Uchida N, Hanawa H, Dan K, Inokuchi K, Shimada T
The BCR/ABL fusion oncogene found in Philadelphia-positive leukemia exists in three principle forms: p190, p210 and p230. P210 BCR/ABL is commonly found in patients with chronic myelogenous leukemia (CML) and is further categorized into b3a2 or b2a2 subtypes on the basis of the BCR breakpoint. Although these 2 subtypes may be clinically heterogeneous, only the b3a2 BCR/ABL gene has been extensively studied at the molecular and cellular levels. In the present study, we compared the in vivo leukemogenic activity of the b3a2 and b2a2 BCR/ABL genes by using lentiviral transduction/transplantation mouse models. Lineage-depleted bone marrow cells of BALB/c mice were transduced with a lentiviral vector including either b2a2 or b3a2 BCR…
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Posted by rob on under Uncategorized |
Authors: Tojo A, Usuki K, Urabe A, Maeda Y, Kobayashi Y, Jinnai I, Ohyashiki K, Nishimura M, Kawaguchi T, Tanaka H, Miyamura K, Miyazaki Y, Hughes T, Branford S, Okamoto S, Ishikawa J, Okada M, Usui N, Tanii H, Amagasaki T, Natori H, Naoe T
Nilotinib is a second-generation BCR-ABL kinase inhibitor with improved potency and selectivity compared to imatinib. A Phase I/II dose-escalation study was designed to evaluate the efficacy, safety, and pharmacokinetics of nilotinib in Japanese patients with imatinib-resistant or -intolerant Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) or relapsed/refractory Ph+ acute lymphoblastic leukemia (ALL). A total of 34 patients were evaluated in this analysis and had a median duration of drug exposure of 293 (range 13-615) days…
Posted by rob on under Uncategorized |
Authors: Kim SH, Choi SJ, Kim YC, Kuh HJ
Indirubin has been identified as a component of a traditional Chinese medicine, Danggui Longhui Wan, which is used for the treatment of chronic myelogenous leukemia. Indirubin inhibits cyclin-dependent kinases (CDKs) and induces cell cycle arrest and apoptosis in cancer cells. Many indirubin derivatives have been studied for their potential anti-solid tumor activity. We have synthesized and evaluated many indirubin derivatives. In order to compare and confirm the potential of our major derivatives as anti-solid tumor agents, we examined their anti-proliferative activity in monolayers, as well as in multicellular spheroids (MCS) cultures of human colorectal cancer cells, DLD-1 and HT-29. The MCS model is an in vitro solid tumor model that is incr…
Posted by rob on under Uncategorized |
Authors: Breccia M, Alimena G
Imatinib mesylate is currently the standard therapy for chronic myeloid leukemia (CML) patients. Despite the remarkable results achieved with imatinib, the emergence of resistance to this drug has become a significant problem. Several strategies have been developed to overcome imatinib resistance, including dose escalation of the drug, combination treatments or novel targeted agents. Nilotinib is a second-generation tyrosine kinase inhibitor 30-50 fold more potent than imatinib with high affinity and selectivity on BCR/ABL, active against a wide range of mutant clones, except T315I mutation. Phase II trials of nilotinib showed high activity in imatinib-resistant or intolerant CML patients; front-line treatment of chronic phase Ph+ CML demonstrated rapid an…
Posted by rob on May 29, 2009 under Uncategorized |
Posted by rob on May 28, 2009 under Uncategorized |
Abstract: The del(15q) chromosomal abnormality is known to occur in acute leukemias, but has rarely been described in chronic myelogenous leukemia (CML). Described here are five cases of CML associated with del(15q): four men and one woman. Bone marrow aspirate smears showed increased blasts in all cases at the time of del(15q) detection, in accelerated phase in two cases and myeloid blast phase in three. Conventional cytogenetic analysis showed t(9;22) and del(15q), as well as other inconsistent clonal abnormalities. All patients received imatinib mesylate; four received additional chemotherapy, and two had allogeneic stem cell transplantation (ASCT). Of the three patients who did not receive ASCT, one died, one was in persistent blast phase, and one was in clinical remission with molecul…
Posted by rob on May 25, 2009 under Uncategorized |
The first formal classification of chronic myeloid neoplasms is credited to William Dameshek, who in 1951 described the concept of “myeloproliferative disorders (MPD)” by grouping together chronic myelogenous leukemia, polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The 2001 World Health Organization (WHO) classification of myeloid malignancies included these MPDs under the broader category of chronic myeloproliferative diseases (CMPD), which also included chronic neutrophilic leukemia, chronic eosinophilic leukemia/hypereosinophilic syndrome (CEL/HES), and “CMPD, unclassifiable.” The revised 2008 WHO classification system featured the following changes: 1) the term “CMPD” was replaced by “myeloproliferative neoplasm (MPN),” 2) mast cell disease was…
Posted by rob on May 20, 2009 under Uncategorized |
Posted by rob on May 15, 2009 under Uncategorized |
A tandem triplication of the long arm of chromosome 1, trp(1)(q), is a rare secondary karyotypic event in hematologic malignancies, and only 27 cases of 1q triplication have been reported in the literature : acute myeloid leukemia/myelodysplastic syndrome (eight cases), lymphoma (nine cases), acute lymphoblastic leukemia (six cases), multiple myeloma (three cases), and Fanconi anemia without other hematologic malignancies (one case). As far as we know, however, there have been no reports of 1q triplication in patients with chronic myelogenous leukemia (CML) or other myeloproliferative neoplasms (MPN). Here, we describe two additional cases of 1q triplication in such myeloid neoplasms. (Source: Cancer Genetics and Cytogenetics)
Posted by rob on May 12, 2009 under Uncategorized |
Authors: Ahmed A, Powers MP, Youker KA, Rice L, Ewton A, Dunphy CH, Chang CC
The mast cell has been associated with fibrosis in many different tissues, organs, and different disease processes including hematopoietic malignancies. Mast cells are often increased in the bone marrow of patients with primary bone marrow disorders, and patients with systemic mastocytosis often have a second concomitant neoplastic disease of the bone marrow. The goals of the current study were to determine the role the mast cell has in the pathogenesis of myeloproliferative neoplasms (MPN) and to correlate the mast cell burden with the degree of reticulin fibrosis. We used computer-assisted image analysis of bone marrow core biopsies stained for mast cell tryptase from patients with myeloproliferative neoplas…
Posted by rob on May 11, 2009 under Uncategorized |
In this study, HA117 gene was investigated whether it could increase the drug resistance in chronic myelogenous myeloid leukemia cell line K562.
Methods:
HA117 was cloned and adenovirus vectors were constructed with the HA117 gene (Adeasy-HA117). K562 cells were infected by Ad-HA117 to get the K562/Ad-HA117 cells with HA117 gene expression. The infection efficiency and the multiplicity of infection (MOI) were detected by fluorescence and flow cytometry. The expression of HA117 gene was detected by RT-PCR. The drug sensitivities of K562/Ad-HA117 cells were detected by Methyl Thiazolyl Tetrazolium (MTT) assay.
Results:
Recombinant adenovirus vectors were constructed and a MOI of 100 is most suitable to infect K562 cells. The infected K562 cells demonstrated in vitro production of HA117 mRN…
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Posted by rob on May 9, 2009 under Uncategorized |
Posted by rob on May 6, 2009 under Uncategorized |
Chronic myelogenous leukemia (CML) is a hematopoietic disorder originating from p210BCR/ABL-transformed stem cells, which begins as indolent chronic phase (CP) but progresses into fatal blast crisis (BC). To investigate molecular mechanism(s) underlying disease evolution, CML-exhibiting p210BCR/ABL transgenic mice were crossed with BXH2 mice that transmit a replication-competent retrovirus. Whereas nontransgenic mice in the BXH2 background exclusively developed acute myeloid leukemia, p210BCR/ABL transgenic littermates developed nonmyeloid leukemias, in which inverse polymerase chain reaction detected 2 common viral integration sites (CISs). Interestingly, one CIS was transgene’s own promoter, which up-regulated p210BCR/ABL expression. The other was the 5′ noncoding region of a transcripti…
Posted by rob on under Uncategorized |
Chronic myelogenous leukemia (CML) is a malignant myeloproliferative disease arising from a hematopoietic stem cell expressing the BCR/ABL fusion protein. Leukemic and dendritic cells (DCs) develop from the same transformed hematopoietic progenitors. How BCR/ABL interferes with the immunoregulatory function of DCs in vivo is unknown. We analyzed the function of BCR/ABL-expressing DCs in a retroviral-induced murine CML model using the glycoprotein of lymphocytic choriomeningitis virus as a model leukemia antigen. BCR/ABL-expressing DCs were found in bone marrow, thymus, spleen, lymph nodes, and blood of CML mice. They were characterized by a low maturation status and induced only limited expansion of naive and memory cytotoxic T lymphocytes (CTLs). In addition, immunization with in vitro&nd…
Posted by rob on under Uncategorized |
