Posted by rob on February 27, 2010 under Uncategorized | 
Conclusions: These single-step, closed-tube assays specifically target mutations associated with resistance to dasatinib or nilotinib. Compared with standard genotyping, such biased genotyping improves the detection of resistance or alternative features via quantitative analysis of the absolute amount of resistance. (Source: Clinical Chemistry)
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Leukemia cutis in a patient with acute myelogenous leukemia: a case report and review of the literature.
Cutis. 2010 Jan;85(1):31-6
Authors: Aguilera SB, Zarraga M, Rosen L
Leukemia cutis is an infiltration of malignant neoplastic leukocytes or their precursors into the epidermis, dermis, or subcutis. These neoplastic cells are derived from abnormal leukocytes in the bone marrow where maturation aberrations occur. Acute myelogenous leukemia (AML) is the second most common cause of leukemia cutis and the most common leukemia among adults. In the elderly population, AML presents a challenge to the medical community because of the number of preexisting comorbid conditions and the safety profile of useful chemotherapeutic agents.
PMID: 20184209 [PubMed - in process]
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Posted by rob on February 26, 2010 under Uncategorized |
Estimation of Multiple Response Rates in Phase II Clinical Trials with Missing Observations.
J Biopharm Stat. 2009 Sep;19(5):791-802
Authors: Chang M
Responses are often correlated in clinical trials. A patient who is not evaluable for a response may still provide some information to the response through his or her status on other responses. Under the assumption of missing at random, we propose the utilization of a self-consistent estimator. We show that the proposed estimators are more efficient than the conventional estimators by asymptotic relative efficiency and simulation study. An example from a Phase II clinical trial on children with chronic myelogenous leukemia is provided.
PMID: 20183444 [PubMed - in process]
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Cord blood stem cell transplantation in a patient with disseminated mucormycosis and acute myelogenous leukemia.
Transpl Infect Dis. 2010 Feb 17;
Authors: Aoki T, Kamezaki K, Miyamoto T, Nagafuji K, Mori Y, Yamauchi T, Takenaka K, Iwasaki H, Harada N, Shimono N, Teshima T, Akashi K
T. Aoki, K. Kamezaki, T. Miyamoto, K. Nagafuji, Y. Mori, T. Yamauchi, K. Takenaka, H. Iwasaki, N. Harada, N. Shimono, T. Teshima, K. Akashi. Cord blood stem cell transplantation in a patient with disseminated mucormycosis and acute myelogenous leukemia. Transpl Infect Dis 2010. All rights reserved.
PMID: 20180927 [PubMed - as supplied by publisher]
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[A patient with acute Philadelphia-chromosome-positive mixed phenotype leukemia developing ecthyma gangrenosum while undergoing combined imatinib mesylate chemotherapy]
Kansenshogaku Zasshi. 2009 Nov;83(6):669-72
Authors: Suzuki K, Sekine T
A 67-year-old woman with acute Philadelphia-chromosome-positive mixed phenotype leukemia developed bilateral periorbital ecthyma gangrenousum (EG) subsequent to periorbital edema while undergoing combined imatinib mesylate (imatinib) chemotherapy. Although initial periorbital edema was considered an imatinib side effect, the lesion deteriorated rapidly with high fever in the neutropenic phase, and the woman died of septic shock. Cultures from blood and exudative fluid grew Pseudomonas aeruginosa, after which EG was diagnosed. EG is a well-recognized emergent cutaneous infection most commonly associated with Pseudomonas aeruginosa bactremia. Because some patients present with EG a few days prior to developing life-threatening septicemia, it is important that EG be diagnosed correctly. Imatinib side effects such as edema are usually tolerable, and imatinib is widely used to treat Philadelphia-chromosome-positive leukemia, particularly in those with acute lymphoblastic leukemia, and neutropenic patients undergoing imatinib therapy are expected to increase in number. Delay in initiating appropriate therapy is correlated with poor outcome, so drug side effects and EG must be carefully differentiated when skin edema with surrounding erythema is noted in neutropenic patients undergoing imatinib therapy.
PMID: 20034323 [PubMed - indexed for MEDLINE]
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Gelatinous transformation of the bone marrow as a late morphological change in imatinib mesylate treated chronic myeloid leukaemia.
Pathology. 2010 Jan;42(1):84-5
Authors: Hong FS, Mitchell CA, Zantomio D
PMID: 20025487 [PubMed - indexed for MEDLINE]
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Successful completion of pregnancy in a patient with chronic myeloid leukemia without active intervention: a case report and review of the literature.
Clin Lymphoma Myeloma. 2009 Aug;9(4):324-7
Authors: Cole S, Kantarjian H, Ault P, Cortés JE
The management of patients with chronic myeloid leukemia (CML) during pregnancy is a matter of continued debate. We present a 21-year-old woman in whom CML was diagnosed during early pregnancy. Because the patient was asymptomatic and desired to carry the pregnancy to term while minimizing fetal exposure to medication, she was observed with no therapy for the duration of her pregnancy. The white blood cell count showed a slow downward trend throughout her pregnancy. She delivered a healthy baby and breast fed for a time before initiating therapy for CML. We reviewed the published case reports of women who had a pregnancy occur in the setting of treatment with imatinib. Given the adverse effects of fetal exposure to imatinib as treatment for the mother with CML, close observation might be an option for selected patients who are diagnosed with CML while pregnant and who have minimal clinical manifestations of CML.
PMID: 19717385 [PubMed - indexed for MEDLINE]
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Posted by rob on February 25, 2010 under Uncategorized |
Therapeutic outcome of chronic myelogenous leukemia (CML) in advanced phases and of Philadelphia chromosome-positive (Ph+) acute leukemias remains dismal, even with tyrosine kinase inhibitors (TKIs) against Bcr-Abl or hematopoietic stem cell transplantation (HSCT) with maximally myeloablative conditioning (MAST). Especially, because patients over 55 years old are not eligible for MAST, the establishment of a treatment strategy for elderly patients with acute/advanced Ph+ leukemias has long been anticipated. We here present our experience with the use of fludarabine (Flu)/busulfan (Bu) 16 conditioning regimen (FB16) and dasatinib maintenance therapy following allogenic bone marrow transplantation (BMT) for two elderly patients with Ph+ acute/advanced leukemia. (Source: Leukemia Research)
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Isolated extramedullary relapse (EMR) of chronic myelogenous leukemia (CML) after bone marrow transplantation (BMT) is rare, seen in only 0.21% of cases . EMR in the central nervous system (CNS) is a rare event, and when seen is more commonly associated with lymphoblastic cells . Only two cases of CNS myeloblastic relapse have been reported previously . To our knowledge, isolated CNS myeloid blastic crisis after allogenic BMT for CML has previously not been reported. (Source: Leukemia Research)
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The advent of molecular medicine has allowed physicians and scientists to decipher some of nature’s mysteries. Few stories are more exhilarating than that of the successes in pediatric acute lymphoblastic leukemia (ALL) and chronic myelogenous leukemia (CML). Indeed, children with ALL are now curable without the need for cranial radiation and imatinib mesylate has changed the landscape of CML therapy . Despite these advances disease recurrence and adverse late effects continue to dampen our celebrations. Enticing dormant cancer stem cells to undergo mitosis and offering risk-directed therapy are current endeavors aimed to overcome these obstacles. (Source: Leukemia Research)
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Chronic myelogenous leukemia (CML) is characterized by a reciprocal chromosomal translocation (9;22) that generates the Bcr-Abl fusion gene. The Ras/Raf-1/MEK/ERK pathway is constitutively activated in Bcr-Abl-transformed cells, and Ras activity enhances the oncogenic ability of Bcr-Abl. However, the mechanism by which Bcr-Abl activates the Ras pathway is not completely understood. Raf kinase inhibitor protein (RKIP) inhibits activation of MEK by Raf-1 and its downstream signal transduction, resulting in blocking the MAP kinase pathway. In the present study, we found that RKIP was depleted in CML cells. We investigated the interaction between RKIP and Bcr-Abl in CML cell lines and Bcr-Abl+ progenitor cells from CML patients. The Abl kinase inhibitors and depletion of Bcr-Abl induced the ex…
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In this study, in vivo circulatory metabolites of meisoindigo in rat plasma, as well as excretory metabolites in rat urine and feces, were identified by liquid chromatography/tandem mass spectrometry (LC/MS/MS). Integration of multiple reaction monitoring with conventional metabolic profiling methodology was adopted to enable a more sensitive detection of in vivo metabolites. By comparing with the MS/MS spectra and retention times of the in vitro reduced metabolites, the major metabolites in rat plasma were proposed to form from 3,3′ double bond reduction, whereas the minor metabolites were formed from reduction followed by N-demethylation, and reduction followed by phenyl mono-oxidation. The major metabolites in the rat urine were proposed to form from reduction followed by phenyl mono-ox…
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Improvement of cytotoxicity of titanocene-functionalized mesoporous materials by the increase of the titanium content.
Dalton Trans. 2010 Mar 14;39(10):2597-2608
Authors: Kaluđerović GN, Pérez-Quintanilla D, Zižak Z, Juranić ZD, Gómez-Ruiz S
The reaction of [Ti(eta(5)-C(5)H(5))(2)Cl(2)] (), with 3-mercaptopropyltrimethoxysilane or 3-mercaptopropyltriethoxysilane in the presence of triethylamine leads to the formation of the thiolate complexes [Ti(eta(5)-C(5)H(5))(2){SCH(2)CH(2)CH(2)Si(OMe)(3)}(2)] () and [Ti(eta(5)-C(5)H(5))(2){SCH(2)CH(2)CH(2)Si(OEt)(3)}(2)] (), respectively. Complexes and have been characterized by traditional methods, in addition, structural studies based on DFT calculations are reported. have been grafted onto dehydroxylated MCM-41 to give the novel materials MCM-41/[Ti(eta(5)-C(5)H(5))(2)Cl(2)] (), MCM-41/[Ti(eta(5)-C(5)H(5))(2){SCH(2)CH(2)CH(2)Si(OMe)(3)}(2)] () and MCM-41/[Ti(eta(5)-C(5)H(5))(2){SCH(2)CH(2)CH(2)Si(OEt)(3)}(2)] () which have been characterized by powder X-ray diffraction, X-ray fluorescence, nitrogen gas sorption, multinuclear MAS NMR spectroscopy, thermogravimetry, UV spectroscopy, SEM and TEM. Materials and present much higher values of Ti wt% (ca. 3%) than (ca. 1%), indicating the higher functionalization rate induced by the substitution of the chloro ligands by the thiolato ligands in the starting titanocene derivatives. The cytotoxicity of the non-functionalized MCM-41 and toward human cancer cell lines such as adenocarcinoma HeLa, human myelogenous leukemia K562 and human malignant melanoma Fem-x has been studied. In addition the cytoxicity of these materials on normal immunocompetent cells such as stimulated (PBMC+PHA) and non-stimulated (PBMC-PHA) peripheral blood mononuclear cells have been also studied. M(50) values (quantity of material needed to inhibit normal cell survival by 50%) of the studied surfaces show that non-functionalized MCM-41 was not active against any of the studied cells, while the functionalized surfaces were active against all the tested human cancer cells. The cytotoxic activity of surfaces and were very similar, however, showed lower cytotoxic activity. This phenomenon indicates that the cytotoxicity of the titanocene-functionalized materials strongly depends on the titanium content.
PMID: 20179853 [PubMed - as supplied by publisher]
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SUZ12 is a candidate target of the non-canonical WNT pathway in the progression of chronic myeloid leukemia.
Genes Chromosomes Cancer. 2010 Feb;49(2):107-18
Authors: Pizzatti L, Binato R, Cofre J, Gomes BE, Dobbin J, Haussmann ME, D’Azambuja D, Bouzas LF, Abdelhay E
Polycomb proteins form multiprotein complexes that repress target genes by chromatin remodeling. In this work, we report that the SUZ12 polycomb gene is over-expressed in bone marrow samples of patients at the blastic phase of chronic myeloid leukemia. We also found a direct interaction between polycomb group genes and the WNT signaling pathway in chronic myeloid leukemia transformation. Electrophoretic mobility shift assay (EMSA), Chromatin immunoprecipitation assay (ChIP), and mass spectrometry assays identified noncanonical WNT pathway members, such as WNT5A and WNT11, bound to the SUZ12 promoter. Immunohistochemistry and immunofluorescence with WNT5A and WNT11 antibodies confirmed nuclear localization. Knockdown of WNTs 1, 5A, and 11 with RNAi approaches showed that WNT members are capable of activating SUZ12 transcription with varying promoter affinities. Finally, we suggest that SUZ12 is blocking cellular differentiation, as SUZ12 knockdown release differentiation programs in chronic myeloid blastic phase (CML-BP) transformed cell line.
PMID: 19847889 [PubMed - indexed for MEDLINE]
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Posted by rob on February 18, 2010 under Uncategorized |
Authors: Lin L, Chen J, Lin Q, Chen W, Chen J, Yao H, Liu A, Lin X, Chen Y
A novel electrochemical biosensor is described for detection of breakpoint cluster region gene and a cellular abl (BCR/ABL) fusion gene in chronic myelogenous leukemia (CML) by using thiolated-hairpin locked nucleic acids (LNA) as the capture probe. The hairpin LNA probe was immobilized on the nanogold (NG)/poly-eriochrome black T (EBT) film-modified glassy carbon electrode (GCE). The immobilized LNA probe could selectively hybridize with its target DNA on LNA/NG/EBT/GCE surface. The immobilization and hybridization of the LNA probe were characterized with cyclic voltammetry and electrochemical impedance spectroscopy. The hybridization of the immobilized LNA probe with the target DNA was detected by differential…
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Cause of death in patients with lower-risk myelodysplastic syndrome.
Cancer. 2010 Feb 16;
Authors: Dayyani F, Conley AP, Strom SS, Stevenson W, Cortes JE, Borthakur G, Faderl S, O’Brien S, Pierce S, Kantarjian H, Garcia-Manero G
BACKGROUND:: The authors have recently shown that a majority of patients with myelodysplastic syndrome (MDS) classified by the International Prognostic Scoring System as lower risk die without transformation to acute myelogenous leukemia (AML). The cause of death (COD) of these patients is not well understood. Identifying the COD could help to guide early therapy decisions. METHODS:: The authors retrospectively analyzed the COD in a cohort of 273 deceased patients with lower-risk MDS according to the International Prognostic Scoring System at presentation to The University of Texas M. D. Anderson Cancer Center from 1980 to 2004. MDS-related death was defined as infection, bleeding, transformation to AML, or disease progression. Remaining CODs were classified as non-MDS-related. RESULTS:: Median age at presentation was 66 years (range, 19-88 years). Overall median survival was 59 weeks (range, 1-831 weeks). All French-American-British leukemia classification subgroups were represented. The percentage of International Prognostic Scoring System low and intermediate-1 groups were 21% and 79%, respectively. The most common cytogenetic abnormality (9%) was del(5q). Patients received supportive care only. The COD was identified as MDS-related in 230 of 273 (84%) patients. The most common disease-related CODs were infection (38%), transformation to AML (15%), and hemorrhage (13%). The most frequent non-disease-related COD was cardiovascular events (19 of 43 patients). CONCLUSIONS:: The majority of patients with low- or intermediate-1 risk MDS will die because of causes related to their underlying disease. Although these results need to be validated in different populations, early therapeutic intervention could be considered in the management of these patients to improve survival. Cancer 2010. (c) 2010 American Cancer Society.
PMID: 20162709 [PubMed - as supplied by publisher]
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Discovery of 8-methoxypyrazino[1,2-a]indole as a New Potent Antiproliferative Agent Against Human Leukemia K562 Cells. A Structure-Activity Relationship Study.
Lett Drug Des Discov. 2009 Jun 1;6(4):298-303
Authors: Romagnoli R, Baraldi PG, Carrion MD, Cruz-Lopez O, Cara CL, Preti D, Tabrizi MA, Balzarini J, Hamel E, Fabbri E, Gambari R
Identification of novel and selective anticancer agents remains an important and challenging goal in pharmacological research. The indole nucleus, frequently encountered as a molecular fragment in natural products and pharmaceutically active compounds, was employed as the initial building block for the synthesis of a series of pyrazino[1,2-a]indoles 1a-k, variably substituted at the 6, 7, 8 and 9-positions. Compound 1e, bearing the methoxy group at the 8-position of the pyrazino[1,2-a]indole nucleus was identified as a novel potent antiproliferative agent against the human chronic myelogenous leukemia K562 cell line, but it was much less active against several other cancer cell lines. Comparison of positional isomers indicated that moving the methoxy group from the 8- to the 7- or 6-position, to furnish compounds 1f and 1g, respectively, yielded inactive compounds. The analysis of structure-activity relationships observed in the series of investigated compounds may represent the basis for the design of more active molecules.
PMID: 20161090 [PubMed - as supplied by publisher]
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MDCT Imaging Findings of Extramedullary Granulocytic Sarcoma of the Heart.
J Thorac Imaging. 2010 Feb;25(1):W14-6
Authors: Tsai J, Lee EY
Granulocytic sarcoma, also known as chloroma, is an uncommon tumor typically seen in patients with acute myelogenous leukemia (AML). Extramedullary cardiac involvement of granulocytic sarcoma is rare and there is a paucity of information regarding its multidetector computed tomography (MDCT) imaging appearance. We present a case of extramedullary granulocytic sarcoma of the heart detected on MDCT in a young adult male with AML. An understanding of how extramedullary granulocytic sarcoma of the heart appears on MDCT may decrease or prevent delays in diagnosing this uncommon, although important, complication from AML.
PMID: 20160585 [PubMed - in process]
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Acute myelogenous leukemia following treatment of invasive cervix carcinoma: A case report and a review of the literature.
J Cancer Res Ther. 2009 Oct-Dec;5(4):302-4
Authors: Samanta DR, Senapati SN, Sharma PK, Mohanty A, Samantaray S
Second malignancy is one of the late complications of long-term cancer survivors, treated with radiation or chemotherapy. Here is a case report on acute myelogenous leukemia, which developed after 63 months following the completion of treatment with surgery and platinum-based chemoradiation in a patient of carcinoma cervix IB. The above-mentioned second malignancy is one of the late sequelae of platinum-based chemoradiation. This case is reported here for documentation because of its rarity.
PMID: 20160368 [PubMed - in process]
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The FLT3 Internal Tandem Duplication Mutation Is a Secondary Target of the Aurora B Kinase Inhibitor AZD1152-HQPA in Acute Myelogenous Leukemia Cells.
Mol Cancer Ther. 2010 Feb 16;
Authors: Grundy M, Seedhouse C, Shang S, Richardson J, Russell N, Pallis M
Aurora kinases play an essential role in orchestrating chromosome alignment, segregation, and cytokinesis during mitotic progression and both aurora-A and B are frequently overexpressed in a variety of human malignancies. In this study, we report the effects of AZD1152-HQPA, a highly selective inhibitor of aurora-B kinase, in acute myeloid leukemia (AML) cell lines and primary samples. We show that AZD1152-HQPA inhibits the phosphorylation of Histone H3 (pHH3) on serine 10 resulting in polyploid cells, apoptosis, and loss of viability in a panel of AML cell lines. We also show that AZD1152-HQPA sensitivity in our cell lines is irrespective of p53 status and the FLT3-ITD-expressing MOLM-13 and MV4-11 cell lines are particularly sensitive to AZD1152-HQPA. Internal tandem duplications (ITD) within the FLT3 tyrosine kinase receptor are found in approximately 25% of AML patients and are associated with a poor prognosis. Here, we report that AZD1152-HQPA directly targets phosphorylated FLT3 along with inhibiting its downstream target phospho-signal transducer and activator of transcription 5 (STAT5) in the FLT3-ITD cell lines. We show pHH3 expression in primary AML blasts and its inhibition by AZD1152-HQPA at low doses in all of our primary samples tested. AZD1152-HQPA inhibits the clonogenic potential of primary AML samples, with FLT3-ITD samples being the most sensitive (P = 0.029). FLT3-ITD primary samples are also more sensitive to pHH3 inhibition (P = 0.022) and are particularly sensitive to pSTAT5 downregulation after treatment with AZD1152-HQPA compared with FLT3 wild-type samples (P = 0.007). We conclude that mutant FLT3 is a secondary target of AZD1152-HQPA and that FLT3-ITD primary samples are particularly sensitive to the drug. Mol Cancer Ther; 9(3); OF1-12.
PMID: 20159992 [PubMed - as supplied by publisher]
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