A Worldwide Support Network For Chronic Myelogenous Leukemia
Posted by rob on January 21, 2010 under Uncategorized | 
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Chronic myelogenous leukemia has been transformed from deadly to nearly always treatable. (Source: NYT)
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Chronic myelogenous leukemia has been transformed from deadly to nearly always treatable. (Source: NYT > Health)
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Conclusions:
None of these genome losses were detected in any of the CML samples with myeloid transformation, chronic phase or controls, indicating that their presence is obligatory for the development of a malignant clone with a lymphoid phenotype. Notably, the coincidental deletions at IGH and TCR regions appear to precede the loss of IKZF1 and/or p16 genes in CML indicating a possible involvement of RAG in these deletions. (Source: BMC Genomics – Latest articles)
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Successful treatment of acute myelogenous leukemia with favorable cytogenetics by reduced-intensity stem cell transplantation.
Int J Hematol. 2010 Jan 20;
Authors: Kondo T, Yasumoto A, Arita K, Sugita JI, Shigematsu A, Okada K, Takahata M, Onozawa M, Kahata K, Takeda Y, Obara M, Yamamoto S, Endo T, Nishio M, Sato N, Tanaka J, Hashino S, Koike T, Asaka M, Imamura M
Acute myelogenous leukemia (AML) with favorable cytogenetics responds well to chemotherapy. If the leukemia relapses, allogenic hematopoietic stem transplantation (allo-HSCT) is considered as a treatment option. Since the efficacy of reduced-intensity stem cell transplantation (RIST) for AML with favorable cytogenetics has not been established, we retrospectively analyzed the outcomes of allo-HSCT in AML patients according to cytogenetic risks. The outcome of allo-HSCT for AML patients with favorable cytogenetics seemed to be superior to that for AML patients with intermediate cytogenetics. In AML patients with favorable cytogenetics, the 3-year overall survival (OS) and relapse-free survival (RFS) rates were 88 and 76%, respectively, in the RIST group. Both the 3-year OS and RFS rates were 81% in the conventional stem cell transplantation (CST) group. The outcome of RIST for AML patients with favorable cytogenetics was comparable to that for patients who received CST despite the more advanced age and greater organ dysfunction in RIST group than in CST group. None of the patients died within 90 days after RIST. Moreover, there was no relapse in patients with favorable cytogenetics who were in hematological remission prior to RIST. Thus, RIST for AML patients with favorable cytogenetics in remission is safe and effective.
PMID: 20087795 [PubMed - as supplied by publisher]
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Natural Killer Cell Consolidation for Acute Myelogenous Leukemia: A Cell Therapy Ready for Prime Time?
J Clin Oncol. 2010 Jan 19;
Authors: Verneris MR, Grupp SA
PMID: 20085932 [PubMed - as supplied by publisher]
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[Intracranial granulocytic sarcoma extending from the posterior fossa to the carotid space via the jugular foramen: a case report]
No Shinkei Geka. 2010 Jan;38(1):53-9
Authors: Baba S, Matsuo T, Ishizaka S, Morikawa M, Suyama K, Nagata I
Granulocytic sarcoma consists of neoplastic granulocytic precursors and myeloblasts. It is a focal lesion seen in 2-10.9% of acute myelogenous leukaemia (AML) patients. It usually develops either concurrently with the AML or after a remission. On rare occasions, it may be an initial manifestation of AML. Most common involvement sites are bone, periostium, soft tissue, lymph nodes and skin. Intracranial granulocytic sarcoma rarely occurs in meningeal or parenchymal form. We present an extremely rare case of intracranial granulocytic sarcoma extending from the posterior fossa to the carotid space via the jugular foramen in a 69 year old female. This form of involvement has not been previously reported. On MRI, the lesion appears isointense compared with normal grey matter in T1 and T2 weighted images and shows homogeneous contrast enhancement. With these findings, it is difficult to differentiate the lesion from other extraaxial tumours such as meningioma, paraganglioma, schwannoma, carcinoma, metastatic tumor, malignant lymphoma. However, granulocytic sarcoma, densely increased tumour cells restrict diffusion and reduce the extracellular volume fraction, tends to be markedly hyperintense on diffusion-weighted MR images and exhibits a marked decrease in ADC values. Therefore, DWI may be helpful in differentiating granulocytic sarcoma from other intracranial lesions.
PMID: 20085103 [PubMed - in process]
Posted by rob on January 17, 2010 under Uncategorized | Comments are off for this article
Authors: Doumic-Jauffret M, Kim PS, Perthame B
We analyze the asymptotic behavior of a partial differential equation (PDE) model for hematopoiesis. This PDE model is derived from the original agent-based model formulated by Roeder (Nat. Med. 12(10):1181-1184, 2006), and it describes the progression of blood cell development from the stem cell to the terminally differentiated state.To conduct our analysis, we start with the PDE model of Kim et al. (J. Theor. Biol. 246(1):33-69, 2007), which coincides very well with the simulation results obtained by Roeder et al. We simplify the PDE model to make it amenable to analysis and justify our approximations using numerical simulations. An analysis of the simplified PDE model proves to exhibit very similar properties to those of the original ag…
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Posted by rob on January 16, 2010 under Uncategorized | Comments are off for this article
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Stability Analysis of a Simplified Yet Complete Model for Chronic Myelogenous Leukemia.
Bull Math Biol. 2010 Jan 14;
Authors: Doumic-Jauffret M, Kim PS, Perthame B
We analyze the asymptotic behavior of a partial differential equation (PDE) model for hematopoiesis. This PDE model is derived from the original agent-based model formulated by Roeder (Nat. Med. 12(10):1181-1184, 2006), and it describes the progression of blood cell development from the stem cell to the terminally differentiated state.To conduct our analysis, we start with the PDE model of Kim et al. (J. Theor. Biol. 246(1):33-69, 2007), which coincides very well with the simulation results obtained by Roeder et al. We simplify the PDE model to make it amenable to analysis and justify our approximations using numerical simulations. An analysis of the simplified PDE model proves to exhibit very similar properties to those of the original agent-based model, even if for slightly different parameters. Hence, the simplified model is of value in understanding the dynamics of hematopoiesis and of chronic myelogenous leukemia, and it presents the advantage of having fewer parameters, which makes comparison with both experimental data and alternative models much easier.
PMID: 20077027 [PubMed - as supplied by publisher]
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Expression of JL1 is an effective adjunctive marker of leukemia cutis.
Arch Pathol Lab Med. 2010 Jan;134(1):95-102
Authors: Park YS, Park SH, Park SJ, Kim Y, Jang KT, Ko YH, Lee MW, Huh JR, Park CS
CONTEXT: Specific differentiation of leukemia cutis (LC) from nonleukemic dermatoses is crucial to ensure proper treatment for the disease. Because of the exceptionally variable histologic features of LC and the frequent nonleukemic dermatoses in leukemia patients, identification of leukemic cells that infiltrate skin lesions is important. Here, we introduce JL1, a novel leukemia-associated surface antigen, which is not expressed in mature human tissue but in cortical thymocytes and small subpopulations of bone marrow hematopoietic precursors. OBJECTIVES: To assess the expression pattern of JL1 in LC and compare it with other commonly used markers. Also, to evaluate the expression of JL1 in other cutaneous lesions that need differential diagnoses. DESIGN: Immunohistochemical staining with anti-JL1 and other commonly used markers for LC was performed on paraffin-embedded skin biopsies from 32 cases of LC with acute lymphoblastic leukemia/lymphoma and acute myelogenous leukemia. Immunohistochemical staining score was evaluated in each case according to the proportion of positive tumor cells found. JL1 staining was also done on 96 reactive or neoplastic cutaneous lesions. RESULTS: JL1 was detected in 7 of 11 acute lymphoblastic leukemia/lymphoma LC (63.6%) and 7 of 21 acute myelogenous leukemia LC (33.3%), with invariably high-staining scores. None of the other cutaneous lesions or normal tissues expressed JL1. The expression pattern of JL1 was not altered in 2 patients with follow-up biopsies. CONCLUSIONS: Our finding that JL1 is expressed exclusively and stably by leukemic cells suggests that it can be used as a useful adjunctive marker for initial diagnosis and follow-up biopsy of LC, particularly in cases of scarce infiltrates.
PMID: 20073611 [PubMed - in process]
Posted by rob on January 14, 2010 under Uncategorized | Comments are off for this article
Clinical Infectious Diseases, Volume 50, Issue 3, Page 405-415, 1 February 2010.
Invasive fungal infections (IFIs) remain an important cause of morbidity and mortality in patients with acute or chronic leukemia. Advances in the pharmacotherapy of fungal infections and a shift in the epidemiological characteristics of fungal pathogens toward fluconazole?resistant Candida species and saprophytic molds have placed a greater emphasis on selection of broader?spectrum agents for empirical therapy of IFIs in this high?risk population. Newer diagnostic modalities, such as the Aspergillus galactomannan test, the 1,3???d?glucan test, and polymerase chain reaction detection of fungal DNA, may facilitate the earlier diagnosis of IFIs, but their role in detecting breakthrough infecti…
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Distribution of the 3-hydroxyl-3-methylglutaryl coenzyme A reductase gene and isoprenoid production in marine-derived Actinobacteria.
FEMS Microbiol Lett. 2009 Dec 19;
Authors: Khan ST, Izumikawa M, Motohashi K, Mukai A, Takagi M, Shin-Ya K
Abstract During the course of our screening program to isolate isoprenoids from marine Actinobacteria, 523 actinobacterial strains were isolated from 18 marine sponges, a tunicate, and two marine sediments. These strains belonged to 21 different genera, but most were members of Streptomyces, Nocardia, Rhodococcus, and Micromonospora. Some Actinobacteria have been reported to use the mevalonate pathway for the production of isoprenoids as secondary metabolites. Therefore, we investigated whether these strains possessed the 3-hydroxyl-3-methylglutaryl coenzyme A reductase (hmgr) gene, which indicates the presence of the mevalonate pathway. As a result, six strains belonging to the genera Streptomyces (SpC080624SC-11, SpA080624GE-02, and Sp080513GE-23), Nocardia (Sp080513SC-18), and Micromonospora (Se080624GE-07 and SpC080624GE-05) were found to possess the hmgr gene, and these genes were highly similar to hmgr genes in isoprenoid biosynthetic gene clusters. Among the six strains, the two strains SpC080624SC-11 and SpA080624GE-02 produced the novel isoprenoids, JBIR-46, -47, and -48, which consisted of phenazine chromophores, and Sp080513GE-23 produced a known isoprenoid, fumaquinone. Furthermore, these compounds showed cytotoxic activity against human acute myelogenous leukemia HL-60 cells.
PMID: 20067528 [PubMed - as supplied by publisher]
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Chronic myeloid leukemia in the tyrosine kinase inhibitor era: what is the best therapy?
Curr Oncol Rep. 2009 Sep;11(5):337-45
Authors: Quintás-Cardama A, Cortes J
Imatinib mesylate, 400 mg/d, is considered standard therapy for managing patients with chronic myeloid leukemia (CML) in chronic phase, yielding high rates of cytogenetic responses that translate into favorable long-term outcomes. However, some patients do not achieve adequate levels of response, lose a previously acquired response, or are forced to discontinue imatinib therapy because of safety reasons. To avoid these outcomes, several approaches are being tested in the frontline setting, including the use of higher imatinib doses or second-generation tyrosine kinase inhibitors such as nilotinib or dasatinib, the latter of which is approved only for managing patients who have imatinib therapy failure. Newer multikinase inhibitors active against multiple ABL1 mutations are also under development for patients in any CML phase who have therapy failure on sequential imatinib and a second-generation tyrosine kinase inhibitor or carry the highly resistant T315I mutation and are not candidates for allogeneic stem cell transplantation. Some of these approaches are expected to improve the outcomes of patients with CML.
PMID: 19679008 [PubMed - indexed for MEDLINE]
Posted by rob on January 5, 2010 under Uncategorized | Comments are off for this article
Clinical Infectious Diseases, Volume 0, Issue 0, Page 000, Latest Articles.
Invasive fungal infections (IFIs) remain an important cause of morbidity and mortality in patients with acute or chronic leukemia. Advances in the pharmacotherapy of fungal infections and a shift in the epidemiological characteristics of fungal pathogens toward fluconazole?resistant Candida species and saprophytic molds have placed a greater emphasis on selection of broader?spectrum agents for empirical therapy of IFIs in this high?risk population. Newer diagnostic modalities, such as the Aspergillus galactomannan test, the 1,3???d?glucan test, and polymerase chain reaction detection of fungal DNA, may facilitate the earlier diagnosis of IFIs, but their role in detecting breakthrough infection an…
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Formulation Optimization of Etoposide Loaded PLGA Nanoparticles by Double Factorial Design and their Evaluation.
Curr Drug Deliv. 2009 Oct 29;
Authors: Yadav KS, Sawant KK
Etoposide is one of the most commonly used drugs in chemotherapy of acute lymphocytic leukemia and acute myelogenous leukaemia. Etoposide has variable oral bioavailability ranging from 24-74% and has terminal half life of 1.5 hours by intravenous route. The conventional parenteral therapy causes inconvenience and pain to the patients as it has to be given through a continuous IV infusion over 24-34 h. The present investigation was aimed at developing etoposide loaded biodegradable nanoparticles which would be a sustained release formulation and replace the conventional therapy of continuous intravenous administration. Nanoparticles were prepared by emulsion solvent evaporation method using high pressure homogenization. The process parameters like homogenization cycles (four) and homogenization pressure (10000 psi) were first optimized using a 32 factorial design based on response Y1(mean particle size of 98+/-1nm). Then a 32 factorial design was carried out to study the effect of two independent variables, ratio of drug and polymer (X1) and surfactant concentration (X2) on the two responses to obtain their optimized values, percentage entrapment efficiency (Y2, 83.12+/-8.3%) and mean particle size (Y3, 105+/-5.4 nm) for Etoposide loaded PLGA Nanoparticles. Contour plots and response surface plots showed visual representation of relationship between the experimental responses and the set of input variables. The adequacy of the regression model was verified by a check point analysis. The zeta potential values ranged between -23.0 to -34.2 mV, indicating stability. Sucrose was used as cryoprotectant during lyophilization. DSC and XRD studies indicated that etoposide was present in the amorphous phase and may have been homogeneously dispersed in the PLGA matrix. The electron micrographs showed spherical, discrete and homogenous particles. Drug release study showed that etoposide loaded PLGA nanoparticles sustained release up to 72h. The release from the nanoparticles followed first order kinetics and mechanism of drug release was Fickian. Stability studies indicated that it was best to store nanoparticle formulations in the freeze dried state at 2-8 degrees C where they remained stable in terms of both size and drug content upto three months.
PMID: 20044908 [PubMed - as supplied by publisher]
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Targeted therapies and autophagy: new insights from chronic myeloid leukemia.
Autophagy. 2009 Oct;5(7):1050-1
Authors: Salomoni P, Calabretta B
Patients who develop chronic myeloid leukemia (CML) are currently treated with tyrosine kinase inhibitors (TKIs), which inhibit the function of the oncogene BCR/Abl. Most CML cells undergo apoptosis when BCR/Abl tyrosine kinase activity is suppressed by TKIs. Cells surviving drug treatment are either stem cells (CML in early phase) or cells with BCR/Abl-dependent or -independent mechanisms of drug resistance (CML in advanced phase). Since survival of these cells is thought to be responsible for disease recurrence, it is critical to find ways to fully eradicate CML stem cells. We have recently shown that when CML cells, including stem cells, are exposed to TKI they activate an autophagic program, which relies on intracellular calcium and is not inhibited by Bcl-2. Pharmacological or RNAi-mediated inhibition of autophagy potentiates the effect of TKI in inducing death of CML cells, including the stem cells. These data strongly suggest that inhibition of autophagy may improve the therapeutic effects of TKIs in the treatment of CML. In addition, they give credence to the idea that in cancer cells autophagy is part of a stereotypic response to stress and specifically to abrogation of their main oncogenic signal(s).
PMID: 19713759 [PubMed - indexed for MEDLINE]
Posted by rob on January 1, 2010 under Uncategorized | Comments are off for this article
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BCR-ABL mutational studies for predicting the response of patients with chronic myeloid leukaemia to second-generation tyrosine kinase inhibitors after imatinib failure.
Hong Kong Med J. 2009 Oct;15(5):365-73
Authors: Kwan TK, Ma ES, Chan YY, Wan TS, Liu HS, Sim JP, Yeung YM, Lie AK, Yip SF
Imatinib is the standard treatment for chronic myeloid leukaemia. BCR-ABL kinase domain mutation is the commonest mechanism implicated in imatinib resistance. In in-vitro studies, kinase domain mutations are variably resistant to second-line agents. We performed BCR-ABL kinase domain mutational studies in 25 patients in five institutions who failed imatinib and were treated with either nilotinib or dasatinib, to see if their mutational status would predict their clinical responses. Kinase domain mutations involving 11 amino acid substitutions were found in 12 (48%) patients. Most patients showed single kinase domain mutations. There was some concordance between reported drug sensitivity patterns and patient responses. Discordant responses could be related to drug dosage variations and unknown BCR-ABL independent mechanisms. The response prediction for patients with multiple kinase domain mutations was challenging and their mutational patterns could change after tyrosine kinase inhibitor therapy. Although BCR-ABL kinase domain mutational analysis has limitations as a means of predicting the clinical response to second-line tyrosine kinase inhibitors, it helps inform therapy decisions in the management of chronic myeloid leukaemia after imatinib failure.
PMID: 19801694 [PubMed - indexed for MEDLINE]
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Efficacy of dasatinib in a chronic myeloid leukemia patient with disease molecular relapse and chronic GVHD after haploidentical BMT: an immunomodulatory effect?
Bone Marrow Transplant. 2009 Sep;44(5):331-2
Authors: Breccia M, Cannella L, Stefanizzi C, Carotti A, Santopietro M, Alimena G
PMID: 19219075 [PubMed - indexed for MEDLINE]
