Posted by rob on October 31, 2009 under Uncategorized | 
Authors: Cankovic M, Whiteley L, Hawley RC, Zarbo RJ, Chitale D
The presence of the JAK2 V617F mutation is now part of clinical diagnostic algorithms, and JAK2 status is routinely assessed when BCR/ABL- chronic myeloproliferative neoplasms (MPNs) are suspected. The aim of this study was to evaluate performance of 3 screening and 1 quantitative method for JAK2 V617F detection. For the study, 43 samples (27 bone marrow aspirates and 16 peripheral blood samples) were selected. The screening assays were the JAK2 Activating Mutation Assay (InVivoScribe, San Diego, CA), JAK2 MutaScreen kit (Ipsogen, Luminy Biotech, Marseille, France), and a home-brew melting curve analysis method. Ipsogen’s JAK2 MutaQuant assay was used for quantification of mutant and wild-type alleles. The limit of detecti…
More
Posted by rob on under Uncategorized |
CONCLUSIONS: This HPLC-UV/DAD method was sufficiently specific and sensitive for imatinib TDM, with no evidence of interference. Our rapid inexpensive HPLC-UV/DAD method that requires only widely available equipment performs well for plasma imatinib assays.
PMID: 19853594 [PubMed - as supplied by publisher] (Source: International Journal of Clinical Chemistry)
More
Posted by rob on under Uncategorized |
Heat shock protein peptide complex 96-based vaccines in melanoma: How far we are, how far we can get.
Hum Vaccin. 2009 Nov 23;5(11)
Authors: di Pietro A, Tosti G, Ferrucci PF, Testori A
Heat shock proteins (HSPs) are highly conserved, stress-induced proteins and function as chaperones stabilizing and delivering peptides. In several preclinical studies, tumor derived HSP-peptide complexes (HSPPCs) has been shown to be able to induce immunity against several malignancies. HSP-based vaccines, indeed, work across tumor types, bypassing the need for the identification of the single immunogenic peptide, and thus emerging as a class of tumor- and patient-specific vaccines. HSPPC-96-based vaccine vitespen((R)) (formerly Oncophage((R))) is the first autologous cancer vaccine made from individual patients’ tumors which not only confirmed its activity in different malignancies (e.g., gastric cancer, colorectal cancer, pancreatic cancer, non-Hodgkin’s lymphoma and chronic myelogenous leukemia), but was also successfully tested in phase III clinical trials in melanoma and kidney cancer. Even more HSPPC-96-based vaccine demonstrated an excellent safety profile, with almost no toxicity. HSP-based vaccines are emerging as a novel therapeutic approach with a suggestive role in cancer therapy.
PMID: 19875926 [PubMed - as supplied by publisher]
More
Posted by rob on under Uncategorized |
Clinical relevance of vascular endothelial growth factor (VEGFA) and VEGF receptor (VEGFR2) gene polymorphism on the treatment outcome following imatinib therapy.
Ann Oncol. 2009 Oct 29;
Authors: Kim DH, Xu W, Kamel-Reid S, Liu X, Jung CW, Kim S, Lipton JH
BACKGROUND: Imatinib could reverse marrow angiogenesis and decrease the plasma level of vascular endothelial growth factor (VEGF) in chronic myeloid leukemia (CML) patients. Methods, materials and patients: The current study investigated the impact of four vascular endothelial growth factor type A (VEGFA) and three vascular endothelial growth factor receptor type 2 (VEGFR2) gene polymorphisms on the outcomes of 228 CML patients following imatinib therapy. VEGFA genotypes such as -2578C>A (rs699947), -460T>C (rs833061), +405G>C (rs2010963) and +936C>T (rs3025039) loci and VEGFR2 genotypes (rs1531289, rs1870377 and rs2305948) were analyzed using matrix-assisted laser desorption/ionization time-of-flight-based method. RESULTS: In single marker analyses, strong correlations were noted between complete cytogenetic response (CCyR) and VEGFR2 genotypes (rs1531289/rs1870377), between treatment failure and VEGFR2 genotype (rs1870377) and between progression to advanced disease and VEGFA genotypes (rs699947/rs833061). Three haplotypes of VEGFR2 gene were generated as follows: GT (46.1%), AT (27.9%) and GA (25.7%). Haplotype analyses showed good correlations between VEGFR2 haplotype and CCyR and treatment failure to imatinib. Multivariate analyses confirmed strong correlations of VEGFR2 polymorphisms (especially rs1531289, rs1870377 or VEGFR2 haplotype) with CCyR, treatment failure and of VEGFA genotype (rs699947) with progression to advanced disease. CONCLUSION: The VEGFR2 gene polymorphism correlates with cytogenetic response, treatment failure following imatinib therapy for CML, while VEGFA genotype correlates with progression to advanced disease.
PMID: 19875757 [PubMed - as supplied by publisher]
More
Posted by rob on under Uncategorized |
TARGETS AND EFFECTORS OF THE CELLULAR RESPONSE TO AURORA KINASE INHIBITOR MK-0457 (VX-680) IN IMATINIB SENSITIVE AND RESISTANT CHRONIC MYELOGENOUS LEUKEMIA.
Biochem Pharmacol. 2009 Oct 26;
Authors: Donato NJ, Feng D, Sun H, Giannola D, Peterson LF, Talpaz M
MK-0457 inhibits aurora, BCR-ABL and other kinases and may be clinically active in imatinib resistant leukemia. To define mediators of MK-0457 responsiveness, kinase inhibitory profiles were examined in multiple cell models of imatinib sensitive and resistant disease. Aurora and BCR-ABL kinase inhibition were consistently measured at 20 – 100nM and 2 – 10muM MK-0457, respectively, but expression of T315I-BCR-ABL and overexpression of Lyn kinase reduced MK-0457 sensitivity. Aurora kinase inhibition was associated with cell cycle restriction and p53 induction and p53-null cells were far less responsive to MK-0457, requiring BCR-ABL inhibitory concentrations for apoptotic activity. In wild-type p53 expressing CML cells MK-0457 sensitivity was modulation by alterations in p53 levels through HDM-2 inhibition and gene silencing. MK-0457 suppressed aurora kinase activity and induced apoptosis in imatinib resistant clinical specimens expressing T315I and other BCR-ABL mutations without effecting BCR-ABL kinase activity. Together, these results suggest that MK-0457 apoptotic activity in CML cells is primarily associated with aurora kinase inhibition but can be altered by multiple molecular changes associated with disease progression or acquisition of imatinib resistance.
PMID: 19874801 [PubMed - as supplied by publisher]
More
Posted by rob on under Uncategorized |
[Prophylaxis use of posaconazole (P) in an hemato-oncology unit: A retrospective study.]
Pathol Biol (Paris). 2009 Oct 26;
Authors: Selvy N, Villiet M, Hansel-Esteller S
OBJECTIVE OF THIS STUDY: The mortality level of leucemic patient’s fungal infections can reach 70 %. Antifungal prophylaxis posaconazole (P) is used during severe and prolonged neutropenia resulting from chemotherapy for acute myelogenous leukemia (AML), myelodysplastic syndrome and after autologous transplant. PATIENTS AND METHODS: We realized a retrospective study in order to assess the efficiency of P. Oral prophylaxy dosage is 200mg every eight hours to beginning before presumed neutropenia. Treatment failure was defined as the occurrence of proven/probable invasive fungal infections (IFI), receipt of any other systemic antifungal agent for suspected IFI or for impossible swallowing and the occurrence of adverse event. The objective is to note down the incidence of proven/probable IFI prevented by P. RESULTS: We included 22 patients of whom 86 % suffered from AML. P was prescribed in IFI prophylaxies during prolonged and severe neutropenia postchemotherapy (72 %) or postautologous transplant (28 %) and initiated 7 days before neutropenia (50 % of cases). The mean treatment period was 18 days. Colonization occurred in one third of patients (43 % of Candida albicans). Esomeprazole (E) 40mg was associated in 64 % of cases. P prophylaxis failed in 50 % of cases. Proven/probable IFI occurred in one case. Different failure causes were: suspected or possible IFI (n=5) and impossible swallowing (n=5). CONCLUSION: P prophylaxis seems to be efficient among these high-risk patients. However, a P tardive initiation, an E association, P administration and resorption difficulties seem to have a importance in successful treatment. It would be interesting to optimize P treatment with plasmatic dosages to ensure efficiency and safety for patients.
PMID: 19864087 [PubMed - as supplied by publisher]
More
Posted by rob on under Uncategorized |
HSPPC-96 vaccine in metastatic melanoma patients: from the state of the art to a possible future.
Expert Rev Vaccines. 2009 Nov;8(11):1513-26
Authors: Tosti G, di Pietro A, Ferrucci PF, Testori A
Heat-shock proteins are highly conserved, stress-induced proteins with chaperone function for trafficking and delivering peptides within the different compartments of the cell. Tumor-derived heat-shock protein-peptide complexes (HSPPCs) can be used for vaccination against malignancies. In particular, the HSPPC-96-based vaccine vitespen (formerly Oncophage) is the first autologous cancer vaccine made from individual patients’ tumors that has shown encouraging results in clinical trials. In Phase I and II clinical trials, this vaccine has shown activity on different malignancies, such as gastric cancer, colorectal cancer, pancreatic cancer, non-Hodgkin’s lymphoma and chronic myelogenous leukemia. In Phase III clinical trials in melanoma and kidney cancer, it demonstrated an excellent safety profile with almost no toxicity. Heat-shock protein-based vaccines can be considered as a novel therapeutic approach with a promising role in cancer management.
PMID: 19863242 [PubMed - in process]
More
Posted by rob on October 24, 2009 under Uncategorized |
Most mental status deficits in patients with chronic myelogenous leukemia (CML) or primary myelodysplastic syndrome (MDS) precede hematopoietic stem cell transplantation (HSCT) and may improve thereafter, according to research published in the October 1st Cancer. Reuters Health Information (Source: Medscape Medical News Headlines)
More
Posted by rob on under Uncategorized |
Authors: Goldblatt M, Huggins JT, Doelken P, Gurung P, Sahn SA
Dasatanib, which has been approved for rescue therapy for patients with imatinib-resistant chronic myelogenous leukemia and Philadelphia chromosome positive acute lymphoblastic leukemia, is a novel, orally available multitargeted kinase inhibitor of BCR-ABL and SRC family kinases (Quintas-Cardama et al, J Clin Oncol 2007;25:3908-14). It binds to both active and inactive conformations of the ABL gene and is 325 times more potent than imatinib in inhibiting the growth of BCR/ABL cells in vitro (Morelock and Sahn, Chest 1999;116:212-21; Huggins and Sahn, Clin Chest Med 2004;25:141-53). Although dasatinib is a generally well-tolerated drug in the treatment of Philadelphia chromosome positive hematopoetic malignancies, pleural e…
More
Posted by rob on under Uncategorized |
F-18 FDG PET/CT Findings in a Case of Gastric Relapse of Acute Myeloblastic Leukemia.
Clin Nucl Med. 2009 Nov;34(11):788-90
Authors: Suga K, Kawakami Y, Hiyama A, Takeda K, Tanizawa Y, Matsunaga N
An isolated extramedullary relapse of acute myelogenous leukemia (AML) after autologous bone marrow transplantation is uncommon. We report the F-18-fluorodeoxyglucose positron emission tomography-computed tomography (F-18 FDG PET/CT) findings in a 50-year-old man with a gastric relapse of AML. This patient had obtained complete remission (CR) of AML in the lumbar bone marrow by autologous bone marrow transplantation and induction chemoradiotherapy 6 years ago, and CR of the meduallary relapse in the bilateral femoral diaphyses by radiotherapy 2 years ago. Regardless of absence of clinical evidence indicative of relapses of AML, FDG PET/CT scan showed the FDG-avid protrusive mass with the maximum standardized uptake of 6.9 in the gastric fundus, which was histologically diagnosed as a relapse by endoscopic biopsy. After radiotherapy to the stomach, the second FDG PET/CT scan showed the disappearance of this FDG-avid gastric mass, and CR of this lesion was endoscopically confirmed. This case indicates that FDG PET/CT scan may be useful for noninvasively detecting a gastric relapse of AML and for monitoring treatment effect.
PMID: 19851176 [PubMed - in process]
More
Posted by rob on October 23, 2009 under Uncategorized |
Clinical Performance of JAK2 V617F Mutation Detection Assays in a Molecular Diagnostics Laboratory: Evaluation of Screening and Quantitation Methods.
Am J Clin Pathol. 2009 Nov;132(5):713-21
Authors: Cankovic M, Whiteley L, Hawley RC, Zarbo RJ, Chitale D
The presence of the JAK2 V617F mutation is now part of clinical diagnostic algorithms, and JAK2 status is routinely assessed when BCR/ABL- chronic myeloproliferative neoplasms (MPNs) are suspected. The aim of this study was to evaluate performance of 3 screening and 1 quantitative method for JAK2 V617F detection. For the study, 43 samples (27 bone marrow aspirates and 16 peripheral blood samples) were selected. The screening assays were the JAK2 Activating Mutation Assay (InVivoScribe, San Diego, CA), JAK2 MutaScreen kit (Ipsogen, Luminy Biotech, Marseille, France), and a home-brew melting curve analysis method. Ipsogen’s JAK2 MutaQuant assay was used for quantification of mutant and wild-type alleles. The limit of detection was 1% for the kit-based screening methods and 10% for the melting curve method. The JAK2 MutaQuant assay demonstrated analytic sensitivity of 0.01%. All 4 methods detected cases of BCR/ABL- MPNs and gave negative results with BCR/ABL+ chronic myelogenous leukemia, multiple myeloma, myelodysplastic syndrome, and normal cases.
PMID: 19846812 [PubMed - in process]
More
Posted by rob on under Uncategorized |
Synthesis, characterization, electrochemical studies and antitumor activity of some new chalcone analogues containing ferrocenyl pyrazole moiety.
Bioorg Chem. 2009 Sep 29;
Authors: Ratković Z, Juranić ZD, Stanojković T, Manojlović D, Vukićević RD, Radulović N, Joksović MD
A series of new alpha,beta-unsaturated conjugated ketones containing ferrocenyl pyrazole unit were synthesized and fully characterized by IR and NMR spectroscopy. Electrochemical characterization of subject compounds was performed by means of cyclic voltametry. The in vitro cytotoxic activity of all the synthesized compounds was studied against cervix adenocarcinoma HeLa, melanoma Fem-x and myelogenous leukemia K562 cell lines by the MTT method. Derivative 1l containing 3-pyridyl moiety exhibited a better cytotoxic activity in the cell growth inhibition of K562 cell lines in comparison with cisplatin as a reference compound.
PMID: 19846191 [PubMed - as supplied by publisher]
More
Posted by rob on under Uncategorized |
A Phase I Study of the Mammalian Target of Rapamycin Inhibitor Sirolimus and MEC Chemotherapy in Relapsed and Refractory Acute Myelogenous Leukemia.
Clin Cancer Res. 2009 Oct 20;
Authors: Perl AE, Kasner MT, Tsai DE, Vogl DT, Loren AW, Schuster SJ, Porter DL, Stadtmauer EA, Goldstein SC, Frey NV, Nasta SD, Hexner EO, Dierov JK, Swider CR, Bagg A, Gewirtz AM, Carroll M, Luger SM
PURPOSE: Inhibiting mammalian target of rapamycin (mTOR) signaling in acute myelogenous leukemia (AML) blasts and leukemic stem cells may enhance their sensitivity to cytotoxic agents. We sought to determine the safety and describe the toxicity of this approach by adding the mTOR inhibitor, sirolimus (rapamycin), to intensive AML induction chemotherapy. EXPERIMENTAL DESIGN: We performed a phase I dose escalation study of sirolimus with the chemotherapy regimen MEC (mitoxantrone, etoposide, and cytarabine) in patients with relapsed, refractory, or untreated secondary AML. RESULTS: Twenty-nine subjects received sirolimus and MEC across five dose levels. Dose-limiting toxicities were irreversible marrow aplasia and multiorgan failure. The maximum tolerated dose (MTD) of sirolimus was determined to be a 12 mg loading dose on day 1 followed by 4 mg/d on days 2 to 7, concurrent with MEC chemotherapy. Complete or partial remissions occurred in 6 (22%) of the 27 subjects who completed chemotherapy, including 3 (25%) of the 12 subjects treated at the MTD. At the MTD, measured rapamycin trough levels were within the therapeutic range for solid organ transplantation. However, direct measurement of the mTOR target p70 S6 kinase phosphorylation in marrow blasts from these subjects only showed definite target inhibition in one of five evaluable samples. CONCLUSIONS: Sirolimus and MEC is an active and feasible regimen. However, as administered in this study, the synergy between MEC and sirolimus was not confirmed. Future studies are planned with different schedules to clarify the clinical and biochemical effects of sirolimus in AML and to determine whether target inhibition predicts chemotherapy response. (Clin Cancer Res 2009;15(21):OF1-8).
PMID: 19843663 [PubMed - as supplied by publisher]
More
Posted by rob on under Uncategorized |
Effects of imatinib mesylate on renin-angiotensin system (RAS) activity during the clinical course of chronic myeloid leukaemia.
J Int Med Res. 2009 Jul-Aug;37(4):1018-28
Authors: Sayitoglu M, Haznedaroğlu IC, Hatirnaz O, Erbilgin Y, Aksu S, Koca E, Adiguzel C, Bayik M, Akalin I, Gülbas Z, Akay M, Unal A, Kaynar L, Ovali E, Yilmaz M, Yenerel M, Dagdas S, Ozet G, Ar C, Aydin Y, Soysal T, Durgun B, Ozcebe O, Tukun A, Ilhan O, Ozbek U
The renin-angiotensin system (RAS) is involved in cell growth, proliferation and differentiation in bone marrow in an autocrine-paracrine manner, and it modulates normal and neoplastic haematopoietic cell proliferation. This study aimed to assess expressions of the RAS components, renin, angiotensinogen and angiotensin-converting enzyme (ACE), during imatinib mesylate treatment of patients with chronic myeloid leukaemia (CML). Expressions of RAS components were studied in patients with CML at the time of diagnosis (n = 83) and at 3, 6 and 12 months after diagnosis (n = 35) by quantitative real-time polymerase chain reaction. De novo CML patients had increased ACE, angiotensinogen and renin mRNA levels and these expression levels decreased following administration of imatinib. The RAS activities were significantly different among Sokal risk groups of CML, highlighting the altered biological activity of RAS in neoplastic disorders. The results of this study confirm that haematopoietic RAS affects neoplastic cell production, which may be altered via administration of tyrosine kinase inhibitors such as imatinib mesylate.
PMID: 19761684 [PubMed - indexed for MEDLINE]
More
Posted by rob on under Uncategorized |
[Chronic myeloid leukemia in the 21st century: biology and treatment]
Rev Invest Clin. 2009 May-Jun;61(3):221-32
Authors: Chávez-González MA, Ayala-Sánchez M, Mayani H
Chronic Myeloid Leukaemia (CML) is a clonal disease, originated at the level of Hematopoietic Stem Cells (HSC) and characterized by the presence of the Philadelphia (Ph) chromosome and its oncogenic product p210(BcrAbl). Such a protein has been shown to be essential for malignant transformation, since it is capable of altering cell adhesion, proliferation and apoptosis. Historically, CML has been treated by using different approaches: arsenic (in the early days), a variety of chemical agents (busulfan, hydroxyurea, cytarabine), cytokines (IFN-alpha, IFNalpha-PEG), hematopoietic cell transplant (HCT), and more recently drugs generated by design (imatinib, nilotinib, dasatinib). All these molecules exert specific effects on HSC and lead to a variety of clinical and biological responses. In this article, we present an overview about hematopoiesis in CML and its implications in the treatment of this disease.
PMID: 19736811 [PubMed - indexed for MEDLINE]
More
Posted by rob on under Uncategorized |
The role of peripheral blood, bone marrow aspirate and especially bone marrow trephine biopsy in distinguishing atypical chronic myeloid leukemia from chronic granulocytic leukemia and chronic myelomonocytic leukemia.
Eur J Haematol. 2009 Oct;83(4):292-301
Authors: Xubo G, Xingguo L, Xianguo W, Rongzhen X, Xibin X, Lin W, Lei Z, Xiaohong Z, Genbo X, Xiaoying Z
OBJECTIVES: To better realize the features of peripheral blood (PB), bone marrow (BM) aspirate and especially BM trephine biopsy in atypical chronic myeloid leukemia (aCML). METHODS: We studied PB, BM smears in 35 cases of aCML and compared with 84 cases of chronic granulocytic leukemia chronic phase (CGL-CP), 39 cases of chronic myelomonocytic leukemia (CMML). In addition, we evaluated characteristics of BM trephine biopsies in 21 cases of aCML and compared with 68 cases of CGL-CP, 20 cases of CMML. RESULTS: All aCML patients presented with leukocytosis (median WBC 17.3 x 10(9)/L), 48% had moderate anemia, and 85% had thrombocytopenia. Values of monocytes, eosinophils, basophils, percentage of immature granulocytes and monocytes (0.63 +/- 0.41 x 10(9)/L, 0.18 +/- 0.16 x 10(9)/L, 0.09 +/-0.08 x 10(9)/L, 6.27 +/- 3.09%, and 2.46 +/- 1.75%, respectively) were useful in distinguishing aCML from CGL-CP and CMML groups. The BM smears showed that striking dysgranulopoieis (100%), dyserythropoiesis (48.6%), percentage of blasts, nucleated erythrocytes, monocytes, eosinophils, and basophils (2.45 +/- 2.06%, 7.76 +/- 2.89%, 1.30 +/- 1.21%, 1.47 +/- 1.60%, and 1.15 +/- 1.08%, respectively) were all important parameters for a diagnosis of aCML. On BM trephine sections, aCML was characterized as hypercellularity, a moderate degree of reticulin fibrosis (71.4%), lymphocytopenia (76.2%), plasmacytopenia (90.5%), abnormal localization of immature precursors (28.5%), and absence of eosinophilia, basophilia, monocytosis. Furthermore, BM imprints, immunohistochemical, and cytochemical staining findings provided important morphological reference to BM trephine sections and made the identification of nucleated cells more convenient. CONCLUSIONS: Besides the findings observed in PB and BM aspirate, features of BM trephine biopsy (including BM trephine section, BM imprint, immunohistochemical, and cytochemical staining) can also aid in the diagnosis of aCML.
PMID: 19500135 [PubMed - indexed for MEDLINE]
More
Posted by rob on October 17, 2009 under Uncategorized |
Microfluidic single cell arrays to interrogate signalling dynamics of individual, patient-derived hematopoietic stem cells.
Lab Chip. 2009 Sep 21;9(18):2659-64
Authors: Faley SL, Copland M, Wlodkowic D, Kolch W, Seale KT, Wikswo JP, Cooper JM
Stem cells hold great promise as a means of treating otherwise incurable, degenerative diseases due to their ability both to self-renew and differentiate. However, stem cell damage can also play a role in the disease with the formation of solid tumors and leukaemias such as chronic myeloid leukaemia (CML), a hematopoietic stem cell (HSC) disorder. Despite recent medical advances, CML remains incurable by drug therapy. Understanding the mechanisms which govern chemoresistance of individual stem cell leukaemias may therefore require analysis at the single cell level. This task is not trivial using current technologies given that isolating HSCs is difficult, expensive, and inefficient due to low cell yield from patients. In addition, hematopoietic cells are largely non-adherent and thus difficult to study over time using conventional cell culture techniques. Hence, there is a need for new microfluidic platforms that allow the functional interrogation of hundreds of non-adherent single cells in parallel. We demonstrate the ability to perform assays, normally performed on the macroscopic scale, within the microfluidic platform using minimal reagents and low numbers of primary cells. We investigated normal and CML stem cell responses to the tyrosine kinase inhibitor, dasatinib, a drug approved for the treatment of CML. Dynamic, on-chip three-color cell viability assays revealed that differences in the responses of normal and CML stem/progenitor cells to dasatinib were observed even in the early phases of exposure, during which time normal cells exhibit a significantly elevated cell death rate, as compared to both controls and CML cells. Further studies show that dasatinib does, however, markedly reduce CML stem/progenitor cell migration in situ.
PMID: 19704981 [PubMed - indexed for MEDLINE]
More
Posted by rob on under Uncategorized |
Isolated extraocular muscle involvement as the ophthalmic manifestation of leukaemia.
Clin Experiment Ophthalmol. 2009 Aug;37(6):609-13
Authors: Kiratli H, Balci KE, Himmetoğlu C, Uner A
BACKGROUND: Clinical and imaging features of patients with orbital leukaemia primarily involving extraocular muscles were evaluated. METHODS: This retrospective case series includes patients with leukaemia whose only ophthalmic manifestation was extraocular muscle enlargement. Demographic data, clinical information on the systemic disease, prominent ocular signs and symptoms, computed tomography and magnetic resonance imaging characteristics, treatments applied and the outcomes were collected. RESULTS: Five patients were diagnosed as leukaemic infiltration of extraocular muscle between 1995 and 2008. The age at presentation ranged between 3 and 61 years. Acute myeloid leukaemia was the diagnosis in two patients, and chronic lymphocytic leukaemia, chronic myeloid leukaemia and biphenotypic acute leukaemia were found in one patient each, respectively. One patient had bilateral involvement. The lateral rectus muscle was affected in four patients and the superior rectus muscle in one case. Restricted ocular motility was the most common finding. In one patient who had no prior history of leukaemia, an incisional biopsy established the diagnosis. All patients received multi-agent chemotherapy. Four patients expired after a rapid decline of the systemic status within a mean period of 7 months. CONCLUSIONS: Leukaemic infiltration of extraocular muscles is a rare and late manifestation of the advanced disease associated with relapse and there seems to be a predilection for the lateral rectus muscle. Systemic prognosis remains dismal despite intensive chemotherapy.
PMID: 19702712 [PubMed - indexed for MEDLINE]
More
Posted by rob on October 15, 2009 under Uncategorized |
Authors: M Veeraputhiran
& K Mangan (Source: Bone Marrow Transplantation)
More
Posted by rob on under Uncategorized |
Progressive Chromatin Repression and Promoter Methylation of CTNNA1 Associated with Advanced Myeloid Malignancies.
Cancer Res. 2009 Oct 13;
Authors: Ye Y, McDevitt MA, Guo M, Zhang W, Galm O, Gore SD, Karp JE, Maciejewski JP, Kowalski J, Tsai HL, Gondek LP, Tsai HC, Wang X, Hooker C, Smith BD, Carraway HE, Herman JG
Complete loss or deletion of the long arm of chromosome 5 is frequent in myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). The putative gene(s) deleted and responsible for the pathogenesis of these poor prognosis hematologic disorders remain controversial. This study is a comprehensive analysis of previously implicated and novel genes for epigenetic inactivation in AML and MDS. In 146 AML cases, methylation of CTNNA1 was frequent, and more common in AML patients with 5q deletion (31%) than those without 5q deletion (14%), whereas no methylation of other 5q genes was observed. In 31 MDS cases, CTNNA1 methylation was only found in high-risk MDS (>/=RAEB2), but not in low-risk MDS (<RAEB2), indicating that CTNNA1 methylation might be important in the transformation of MDS to AML. CTNNA1 expression was lowest in AML/MDS patients with CTNNA1 methylation, although reduced expression was found in some patients without promoter methylation. Repressive chromatin marks (H3K27me3) at the promoter were identified in CTNNA1-repressed AML cell lines and primary leukemias, with the most repressive state correlating with DNA methylation. These results suggest progressive, acquired epigenetic inactivation at CTNNA1, including histone modifications and promoter CpG methylation, as a component of leukemia progression in patients with both 5q- and non-5q- myeloid malignancies. [Cancer Res 2009;69(21):OF1-9].
PMID: 19826047 [PubMed - as supplied by publisher]
More
