Posted by rob on June 15, 2011 under Uncategorized | 
We present a case of palatal melanosis related to imatinib therapy for chronic myelogenous leukemia. This case is reported to add to the sparse literature concerning mucosal reactions related to this medication.
PMID: 21635826 [PubMed - in process] (Source: Dermatol Online J)
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NCCN has released the NCCN Patient Guidelines for Chronic Myelogenous Leukemia, available free of charge on NCCN.com. NCCN Patient Guidelines are a tool to help patients and their caregivers take a more active role in treatment decisions.
FORT WASHINGTON, PA – The National Comprehensive Cancer Network® (NCCN®), with the support of the NCCN Foundation, recently announced the latest addition to the library of NCCN Guidelines for Patients™, the NCCN Patient Guidelines™ for Chronic Myelogenous … (Source: National Comprehensive Cancer Network)
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Cokeromyces recurvatus is a dimorphic zygomycete with histologic morphology similar to Coccidioides immitis. A 66-year-old man who was status-post bone marrow transplantation for chronic myelogenous leukemia was hospitalized with new onset rash, nausea, and vomiting and subsequently expired. A sputum culture collected on the day of death revealed heavy growth of C. recurvatus 6 days after collection. At autopsy, microscopic examination of the lungs revealed numerous thick-walled, nonbudding spherules ranging in size from 40 to 80 µm. Initial immunohistochemical staining of the formalin-fixed lung tissue was positive for Coccidioides . Additional immunoperoxidase staining revealed the organisms were consistent with a zygomycete fungus, compatible with C. recurvatus infection. Polymera…
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The National Comprehensive Cancer Network® (NCCN®), with the support of the NCCN Foundation, recently announced the latest addition to the library of NCCN Guidelines for Patients™, the NCCN Patient Guidelines™ for Chronic Myelogenous Leukemia. This resource is a patient-friendly, easy-to-understand translation of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines™) for Chronic Myelogenous Leukemia (CML), which physicians use when determining appropriate cancer treatment… (Source: Health News from Medical News Today)
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(Source: Journal of Clinical Oncology)
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Content Type Journal ArticlePages 1-3DOI 10.1007/s00277-011-1269-1Authors
Bo Cai, Department of Hematology, General Hospital of People’s Liberation Army, 28 Fuxing Road, Beijing, 100853 ChinaWeidong Yang, Department of Hematology, Hospital of Anyang District, Anyang, Henan, ChinaYu Zhao, Department of Hematology, General Hospital of People’s Liberation Army, 28 Fuxing Road, Beijing, 100853 ChinaLei Yuan, Department of Hematology, General Hospital of People’s Liberation Army, 28 Fuxing Road, Beijing, 100853 ChinaLili Wang, Department of Hematology, General Hospital of People’s Liberation Army, 28 Fuxing Road, Beijing, 100853 ChinaLi Gao, Department of Hematology, General Hospital of People’s Liberation Army, 28 Fuxing Road, Beijing, 100853 ChinaNan Wang, Department of Hematolo…
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AbstractThe present study is designed to assess if exosomes released from Chronic Myelogenous Leukemia (CML) cells may modulate angiogenesis. We have isolated and characterized the exosomes generated from LAMA84 CML cells and demonstrated that addition of exosomes to human vascular endothelial cells (HUVEC) induces an increase of both ICAM?1 and VCAM?1 cell adhesion molecules and interleukin?8 expression. The stimulation of cell?cell adhesion molecules was paralleled by a dose?dependent increase of adhesion of CML cells to a HUVEC monolayer. We further showed that the treatment with exosomes from CML cells caused an increase in endothelial cell motility accompanied by a loss of VE?cadherin and ??catenin from the endothelial cell surface. Functional characterization of exosom…
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We describe a newborn female with a de novo interstitial deletion of chromosome 21q21.1?22.12 including the RUNX1 gene who had developmental delay, multiple congenital anomalies, tetralogy of Fallot, anemia, and chronic thromobocytopenia requiring frequent platelet transfusions from birth. Because of her physical and hematologic abnormalities, she was tested for Fanconi anemia (FA). Lymphocytes and fibroblasts from this patient demonstrated increased chromosome breakage with exposure to the clastogen mitomycin C, but not, in contrast to most FA patients, to diepoxybutane. Further testing by Western analysis and complementation testing did not show a defect in the function of known Fanconi proteins. Her constitutional deletion was later found to span 13.2?Mb by chromosome microarray ana…
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Conclusion
The prospect for long-term survival is excellent for 2-year survivors of allogeneic HCT. However, life expectancy remains lower than expected. Performance of HCT earlier in the course of disease, control of GVHD, enhancement of immune reconstitution, less toxic regimens, and prevention and early treatment of late complications are needed. (Source: Journal of Clinical Oncology)
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Progression of chronic myelogenous leukemia (CML) to accelerated (AP) and blast phase (BP) is because of secondary molecular events, as well as additional cytogenetic abnormalities. On the basis of the detection of JAK2, CBL, CBLB, TET2, ASXL1, and IDH1/2 mutations in myelodysplastic/myeloproliferative neoplasms, we hypothesized that they may also contribute to progression in CML. We screened these genes for mutations in 54 cases with CML (14 with chronic phase, 14 with AP, 20 with myeloid, and 6 with nonmyeloid BP). We identified 1 CBLB and 2 TET2 mutations in AP, and 1 CBL, 1 CBLB, 4 TET2, 2 ASXL1, and 2 IDH family mutations in myeloid BP. However, none of these mutations were found in chronic phase. No cases with JAK2V617F mutations were found. In 2 cases, TET2 mutations were found conc…
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Abstract Chronic myelogenous leukemia, BCR-ABL1+ (CML) is a myeloproliferative neoplasm defined by the presence of the BCR-ABL fusion gene and a t(9;22)(q34;q11) cytogenetic abnormality. Its natural history is that of inexorable progression to an acute
leukemia (blast crisis) after a prolonged chronic phase. The recent development of imatinib and other inhibitors of BCR-ABL tyrosine kinase activity has dramatically altered the clinical course of CML, with long-term remissions in most patients
treated early in the course of the disease. Monitoring of resistance to therapy and progression on therapy are critical in
the current management of the disease. Problems facing the diagnostic pathologist in this “Age of Imatinib” include accurate
diagnosis and determination of CML …
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Imatinib Is Effective in Children With Previously Untreated Chronic Myelogenous Leukemia in Early Chronic Phase: Results of the French National Phase IV Trial.
J Clin Oncol. 2011 Jun 13;
Authors: Millot F, Baruchel A, Guilhot J, Petit A, Leblanc T, Bertrand Y, Mazingue F, Lutz P, Vérité C, Berthou C, Galambrun C, Bernard F, Yacouben K, Bordigoni P, Edan C, Reguerre Y, Couillault G, Méchinaud F, Cayuela JM, Guilhot F
PURPOSE Imatinib is the standard of care in adults with chronic myeloid leukemia (CML) in chronic phase (CP). Only a few studies to assess efficacy in children have been performed. We report on the results of the French prospective trial (ClinicalTrials.gov identifier NCT00845221) conducted in children and adolescents with newly diagnosed CML in CP. PATIENTS AND METHODS A total of 44 patients from age 10 months to 17 years with newly diagnosed CML in CP received daily imatinib 260 mg/m(2). Progression-free survival, responses, and tolerance were evaluated. Results With a median follow-up times of 31 months (range, 11 to 64 months), the estimated progression-free survival rate at 36 months was 98% (95% CI, 85% to 100%). A complete hematologic response was achieved in 98% of the patients. The rates of complete cytogenetic response (CCyR) and major molecular response (MMR) were 61% and 31% at 12 months, respectively. During follow-up, CCyR and MMR were achieved in 36 children (77%) and 25 children (57%), respectively. Overall, 30% of the patients discontinued imatinib, mainly because of unsatisfactory response. The most common adverse events were neutropenia and musculoskeletal events. CONCLUSION Imatinib is effective in children with CML in CP with response rates similar to rates reported in adults. The adverse effects are acceptable, but larger follow-up studies are required to fully assess the long-term impact.
PMID: 21670449 [PubMed - as supplied by publisher]
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Myelodysplastic syndromes: the role of the immune system in pathogenesis.
Leuk Lymphoma. 2011 Jun 12;
Authors: Warlick ED, Miller JS
The myelodysplastic syndromes (MDS) represent a complex spectrum of clonal hematopoietic stem cell disorders manifested by cytopenias, risk of infection, and variable risk of progression to acute myelogenous leukemia. Several theories of MDS pathogenesis exist, with contributions of genetic, epigenetic, apoptotic, differentiation, and cytokine milieu abnormalities. Immune dysregulation has also been implicated in MDS pathogenesis. In some forms of MDS it is evident that immune dysregulation may be a primary pathophysiologic abnormality, while in others the abnormal immune function may represent only a small part of the pathologic puzzle. We review the current literature regarding natural killer (NK) cell, Tcell, and myeloid derived suppressor cell abnormalities in the spectrum of MDS.
PMID: 21663505 [PubMed - as supplied by publisher]
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Study of Methylation Levels of Parkin Gene Promoter in Parkinson’s Disease Patients.
Int J Neurosci. 2011 Jun 10;
Authors: Cai M, Tian J, Zhao GH, Luo W, Zhang BR
ABSTRACT Mutations in the parkin gene have been significantly linked to autosomal recessive juvenile parkinsonism (ARJP). In addition to its association with ARJP, loss of heterozygosity of parkin has been found in several types of malignant tumors, including ovarian, breast, and hepatocellular tumors. Abnormal methylation of parkin promoter was observed in patients with acute lymphoblastic leukemia and chronic myelogenous leukemia in lymphoid blast crisis. We hypothesized that hypermethylation of the parkin promoter might reduce the expression of parkin, which would contribute to the pathogenesis of parkinson’s disease (PD) in idiopathic patients and parkin heterozygotes. In this study, we analyzed samples from 17 PD patients with heterozygous parkin mutations, 17 PD patients without parkin mutations, and 10 normal controls. We determined the levels of methylation of the parkin gene promoter in each group using bisulfite genomic sequencing of a region containing 33 CpG sites in the CpG island of the parkin promoter. The methylation levels indicated hypomethylation, and there were no significant differences in the incidence of CpG site methylation among three groups (P > 0.05). These results suggest that the methylation mechanism is unlikely to play a role in the pathogenesis and development of PD.
PMID: 21663383 [PubMed - as supplied by publisher]
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Functional phosphoproteomic analysis reveals cold-shock domain protein A to be a Bcr-Abl effector-regulating proliferation and transformation in chronic myeloid leukemia.
Cell Death Dis. 2010;1:e93
Authors: Sears D, Luong P, Yuan M, Nteliopoulos G, Man YK, Melo JV, Basu S
One proposed strategy to suppress the proliferation of imatinib-resistant cells in chronic myeloid leukemia (CML) is to inhibit key proteins downstream of Bcr-Abl. The PI3K/Akt pathway is activated by Bcr-Abl and is specifically required for the growth of CML cells. To identify targets of this pathway, we undertook a proteomic screen and identified several proteins that differentially bind 14-3-3, dependent on Bcr-Abl kinase activity. An siRNA screen of candidates selected by bioinformatics analysis reveals cold-shock domain protein A (CSDA), shown previously to regulate cell cycle progression in epithelial cells, to be a positive regulator of proliferation in a CML cell line. We show that Akt can phosphorylate the serine 134 residue of CSDA but, downstream of Bcr-Abl activity, this modification is mediated through the activation of MEK/p90 ribosomal S6 kinase (RSK) signaling. Inhibition of RSK, similarly to treatment with imatinib, blocked proliferation specifically in Bcr-Abl-positive leukemia cell lines, as well as cells from CML patients. Furthermore, these primary CML cells showed an increase in CSDA phosphorylation. Expression of a CSDA phospho-deficient mutant resulted in the decrease of Bcr-Abl-dependent transformation in Rat1 cells. Our results support a model whereby phosphorylation of CSDA downstream of Bcr-Abl enhances proliferation in CML cells to drive leukemogenesis.
PMID: 21368869 [PubMed - indexed for MEDLINE]
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