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https://www.readbyqxmd.com/read/28212374/the-effect-of-body-mass-index-at-diagnosis-on-clinical-outcome-in-children-with-newly-diagnosed-acute-lymphoblastic-leukemia
#1
H M Eissa, Y Zhou, J C Panetta, E K Browne, S Jeha, C Cheng, M V Relling, D Campana, C-H Pui, H Inaba
The impact of body mass index (BMI) at diagnosis on treatment outcome in children with acute lymphoblastic leukemia (ALL) is controversial. We studied 373 children with ALL enrolled on the Total XV study, which prospectively used minimal residual disease (MRD) for risk assignment. MRD on day 19 and at the end of remission induction (day 46), cumulative incidence of relapse/refractory disease (CIR), event-free survival (EFS) and overall survival (OS) were evaluated using sets of four, three and two subgroups based on BMI at diagnosis, along with BMI percentile change during remission induction...
February 17, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28212370/the-evolution-of-allogeneic-stem-cell-transplant-for-children-and-adolescents-with-acute-myeloid-leukemia
#2
Allyson Flower, Mitchell S Cairo
Survival rates in subsets of pediatric patients who have acute myeloid leukemia (AML) with favorable risk features are now greater than 90%. However, outcomes for patients with high-risk (HR) features remain unacceptably poor. As novel technologies for the identification of HR biomarkers and the detection of residual disease are developed, risk stratification and the application of allogeneic hematopoietic stem cell transplant (HSCT) are evolving. HSCT has been shown to benefit subpopulations of pediatric patients with AML, including those with HR cytogenetic translocations, genetic mutations, and/or residual disease after induction...
January 2017: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/28212262/molecular-cytogenetic-approach-to-characterize-novel-and-cryptic-chromosome-abnormalities-in-childhood-myeloid-malignances-of-fanconi-anemia
#3
Maria L R Borges, Roberto R Capela de Matos, Bethânia D A Silva Amaral, Eliane M Soares-Ventura, Edinalva P Leite, Mariluze O D Silva, Maria T M Nogueira Cornélio, Maria L M Silva, Thomas Liehr, Terezinha D J Marques-Salles
Myeloid malignancies can be either primary or secondary, whether or not a specific cause can be determined. Fanconi anemia (FA), a rare constitutional bone marrow failure, usually presents an increased possibility of clonal evolution, due to the increase in chromosomal instability, TP53 activation, and cell death. The evolution of FA may include aplastic anemia by the progressive failure of the bone marrow and myelod neoplasias, such as acute myeloid leukemia and myelodysplastic syndrome. Chromosome abnormalities, particularly of chromosomes, 1, 3, and 7, during the aplastic phase of the disease are predictive of evolution to acute myeloid leukemia/myelodysplastic syndrome...
March 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28212112/cancer-as-robust-intrinsic-state-shaped-by-evolution-a-key-issues-review
#4
Ruoshi Yuan, Xiaomei Zhu, Gaowei Wang, Site Li, Ping Ao
Cancer is a complex disease: its pathology cannot be properly understood in terms of independent players-genes, proteins, molecular pathways, or their simple combinations. This is similar to many-body physics of a condensed phase that many important properties are not determined by a single atom or molecule. The rapidly accumulating large 'omics' data also require a new mechanistic and global underpinning to organize for rationalizing cancer complexity. A unifying and quantitative theory was proposed by some of the present authors that cancer is a robust state formed by the endogenous molecular-cellular network, which is evolutionarily built for the developmental processes and physiological functions...
February 17, 2017: Reports on Progress in Physics
https://www.readbyqxmd.com/read/28211939/allogeneic-hematopoietic-cell-transplantation-for-primary-refractory-acute-lymphoblastic-leukemia-a-report-from-the-acute-leukemia-working-party-of-the-ebmt
#5
Jiří Pavlů, Myriam Labopin, Anna K Zoellner, Ioanna Sakellari, Matthias Stelljes, Jürgen Finke, Renato Fanin, Gernot Stuhler, Boris V Afanasyev, Adrian J Bloor, Achilles Anagnostopoulos, Mohamad Mohty, Sebastian Giebel, Arnon Nagler
BACKGROUND: Patients with primary refractory acute lymphoblastic leukemia (PREF ALL) who fail to achieve a complete remission (CR) after ≥2 courses of chemotherapy have a dismal prognosis without undergoing allogeneic hematopoietic cell transplantation (HCT). To the authors' knowledge, there currently are no data regarding factors influencing transplantation outcomes. METHODS: The authors retrospectively studied outcomes of transplantation for cases of PREF ALL reported to European Society for Blood and Marrow Transplantation registry...
February 17, 2017: Cancer
https://www.readbyqxmd.com/read/28211886/a-novel-approach-for-the-identification-of-efficient-combination-therapies-in-primary-human-acute-myeloid-leukemia-specimens
#6
I Baccelli, J Krosl, G Boucher, I Boivin, V-P Lavallée, J Hébert, S Lemieux, A Marinier, G Sauvageau
Appropriate culture methods for the interrogation of primary leukemic samples were hitherto lacking and current assays for compound screening are not adapted for large-scale investigation of synergistic combinations. In this study, we report a novel approach that efficiently distills synthetic lethal interactions between small molecules active on primary human acute myeloid leukemia (AML) specimens. In single-dose experiments and under culture conditions preserving leukemia stem cell activity, our strategy considerably reduces the number of tests needed for the identification of promising compound combinations...
February 17, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28211885/the-novel-bmi-1-inhibitor-ptc596-downregulates-mcl-1-and-induces-p53-independent-mitochondrial-apoptosis-in-acute-myeloid-leukemia-progenitor-cells
#7
Y Nishida, A Maeda, M J Kim, L Cao, Y Kubota, J Ishizawa, A AlRawi, Y Kato, A Iwama, M Fujisawa, K Matsue, M Weetall, M Dumble, M Andreeff, T W Davis, A Branstrom, S Kimura, K Kojima
Disease recurrence is the major problem in the treatment of acute myeloid leukemia (AML). Relapse is driven by leukemia stem cells, a chemoresistant subpopulation capable of re-establishing disease. Patients with p53 mutant AML are at an extremely high risk of relapse. B-cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) is required for the self-renewal and maintenance of AML stem cells. Here we studied the effects of a novel small molecule inhibitor of BMI-1, PTC596, in AML cells. Treatment with PTC596 reduced MCL-1 expression and triggered several molecular events consistent with induction of mitochondrial apoptosis: loss of mitochondrial membrane potential, BAX conformational change, caspase-3 cleavage and phosphatidylserine externalization...
February 17, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28211619/intravoxel-incoherent-motion-diffusion-weighted-imaging-of-bone-marrow-in-patients-with-acute-myeloid-leukemia-a-pilot-study-of-prognostic-value
#8
Jinliang Niu, Wenjin Li, Hongwei Wang, Wenqi Wu, Tong Gong, Ning Huang, Jun Wang, Yan Qi
PURPOSE: To investigate the value of intravoxel incoherent motion (IVIM) parameters in evaluation of prognosis in patients with acute myeloid leukemia (AML) before treatment. MATERIALS AND METHODS: Fifty-three patients before standard chemotherapy underwent MRI scans at 1.5 Tesla using conventional diffusion weighted imaging (DWI) and IVIM (b = 0, 10, 25, 50, 100, 200, 400, 600, 800, 1000, 1200 s/mm(2) ) in the sagittal plane covering the lumbar bone marrow...
February 17, 2017: Journal of Magnetic Resonance Imaging: JMRI
https://www.readbyqxmd.com/read/28211293/hfe-gene-mutation-and-iron-overload-in-egyptian-pediatric-acute-lymphoblastic-leukemia-survivors-a-single-center-study
#9
Farida H El-Rashedi, Mahmoud A El-Hawy, Sally M El-Hefnawy, Mona M Mohammed
BACKGROUND: Hereditary hemochromatosis gene (HFE) mutations have a role in iron overload in pediatric acute lymphoblastic leukemia (ALL) survivors. We aimed to evaluate the genotype frequency and allelic distribution of the two HFE gene mutations (C282Y and H63D) in a sample of Egyptian pediatric ALL survivors and to detect the impact of these two mutations on their iron profile. PATIENTS AND METHODS: This study was performed on 35 ALL survivors during their follow-up visits to the Hematology and Oncology Unit, Pediatric Department, Menoufia University Hospitals...
February 17, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/28210842/uric-acid-as-a-novel-biomarker-for-bone-marrow-function-and-incipient-hematopoietic-reconstitution-after-aplasia-in-patients-with-hematologic-malignancies
#10
Sebastian P Haen, Vicky Eyb, Nora Mirza, Aline Naumann, Andreas Peter, Markus W Löffler, Christoph Faul, Wichard Vogel, Wolfgang A Bethge, Hans-Georg Rammensee, Lothar Kanz, Martin Heni
PURPOSE: Prolonged aplasia and graft failure (GF) represent life-threatening complications after hematopoietic cell transplantation (HCT) requiring suitable biomarkers for early detection and differentiation between GF and poor graft function (PGF). Uric acid (UA) is a strong immunological danger signal. METHODS: Laboratory results were analyzed from patients undergoing either allogeneic or autologous HCT or induction chemotherapy for acute leukemia (n = 50 per group, n = 150 total)...
February 16, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28210257/kinetics-of-cytotoxic-lymphocytes-reconstitution-after-induction-chemotherapy-in-elderly-aml-patients-reveals-progressive-recovery-of-normal-phenotypic-and-functional-features-in-nk-cells
#11
Jérôme Rey, Cyril Fauriat, Eloïse Kochbati, Florence Orlanducci, Aude Charbonnier, Evelyne D'Incan, Pascale Andre, François Romagne, Bernadette Barbarat, Norbert Vey, Daniel Olive
NK cells are defective in acute myeloid leukemia (AML) at diagnosis. Here, we studied the kinetic of expression of the major activating and inhibitory receptors of NK, CD8 T, and γδ T cells in patients undergoing chemotherapy (CT) for the treatment of AML (n = 29). We showed that NK cells are the main affected population at diagnosis and that expression of activating receptors is partially restored within a few weeks after CT. CD8 T cells and γδ T cells are only weakly affected at diagnosis. Killer cell immunoglobulin-like receptor expression by NK cells, but not NKG2A and CD85j, was downregulated...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28210006/a-novel-lsd1-inhibitor-ncd38-ameliorates-mds-related-leukemia-with-complex-karyotype-by-attenuating-leukemia-programs-via-activating-super-enhancers
#12
N Sugino, M Kawahara, G Tatsumi, A Kanai, H Matsui, R Yamamoto, Y Nagai, S Fujii, Y Shimazu, M Hishizawa, T Inaba, A Andoh, T Suzuki, A Takaori-Kondo
Lysine-specific demethylase 1 (LSD1) regulates gene expression by affecting histone modifications and is a promising target for acute myeloid leukemia (AML) with specific genetic abnormalities. Novel LSD1 inhibitors, NCD25 and NCD38, inhibited growth of MLL-AF9 leukemia as well as erythroleukemia, megakaryoblastic leukemia and myelodysplastic syndromes (MDS) overt leukemia cells in the concentration range that normal hematopoiesis was spared. NCD25 and NCD38 invoked the myeloid development programs, hindered the MDS and AML oncogenic programs, and commonly upregulated 62 genes in several leukemia cells...
February 17, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28210005/mll-is-essential-for-nup98-hoxa9-induced-leukemia
#13
Y Shima, M Yumoto, T Katsumoto, I Kitabayashi
Rearrangements involving the NUP98 gene resulting in fusions to several partner genes occur in acute myeloid leukemia and myelodysplastic syndromes. This study demonstrates that the second FG repeat domain of the NUP98 moiety of the NUP98-HOXA9 fusion protein is important for its cell immortalization and leukemogenesis activities. We demonstrate that NUP98-HOXA9 interacts with MLL via this FG repeat domain and that, in the absence of MLL, NUP98-HOXA9-induced cell immortalization and leukemogenesis are severely inhibited...
February 17, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28209720/acquired-expression-of-cbl-q367p-in-mice-induces-dysplastic-myelopoiesis-mimicking-chronic-myelomonocytic-leukemia
#14
Yuichiro Nakata, Takeshi Ueda, Akiko Nagamachi, Norimasa Yamasaki, Ken-Ichiro Ikeda, Yasuyuki Sera, Keiyo Takubo, Akinori Kanai, Hideaki Oda, Masashi Sanada, Seishi Ogawa, Kohichiro Tsuji, Yasuhiro Ebihara, Linda Wolff, Zen-Ichiro Honda, Toshio Suda, Toshiya Inaba, Hiroaki Honda
Chronic myelomonocytic leukemia (CMML) is a hematological malignancy characterized by uncontrolled proliferation of dysplastic myelomonocytes and frequent progression to acute myeloid leukemia (AML). We identified mutations in the Cbl gene, which encodes a negative regulator of cytokine signaling, in a subset of CMML patients. To investigate the contribution of mutant Cbl in CMML pathogenesis, we generated conditional knock-in mice for Cbl that express wild-type Cbl in a steady state and inducibly express Cbl(Q367P) , a CMML-associated Cbl mutant...
February 16, 2017: Blood
https://www.readbyqxmd.com/read/28209659/hyperlipidemia-is-a-risk-factor-for-osteonecrosis-in-children-and-young-adults-with-acute-lymphoblastic-leukemia
#15
Signe Sloth Mogensen, Kjeld Schmiegelow, Kathrine Grell, Birgitte Klug Albertsen, Peder Skov Wehner, Peter Kampmann, Thomas Leth Frandsen
No abstract text is available yet for this article.
February 16, 2017: Haematologica
https://www.readbyqxmd.com/read/28209655/mutational-analysis-in-serial-marrow-samples-during-azacitidine-treatment-in-patients-with-post-transplant-relapse-of-acute-myeloid-leukemia-or-myelodysplastic-syndromes
#16
Janghee Woo, Nicholas P Howard, Barry E Storer, Min Fang, Cecilia C Yeung, Bart L Scott, H Joachim Deeg
No abstract text is available yet for this article.
February 16, 2017: Haematologica
https://www.readbyqxmd.com/read/28209616/octn1-is-a-high-affinity-carrier-of-nucleoside-analogs
#17
Christina Drenberg, Alice A Gibson, Stanley Pounds, Lei Shi, Dena Rhinehart, Lie Li, Shuiying Hu, Guoqing Du, Anne T Nies, Matthias Schwab, Navjotsingh Pabla, William Blum, Tanja A Gruber, Sharyn D Baker, Alex Sparreboom
Resistance to xenobiotic nucleosides used to treat acute myeloid leukemia (AML) and other cancers remains a major obstacle to clinical management. One process suggested to participate in resistance is reduced uptake into tumor cells via nucleoside transporters, although precise mechanisms are not understood. Through transcriptomic profiling, we determined that low expression of the ergothioneine transporter OCTN1 (SLC22A4; ETT) strongly predicts poor event-free survival and overall survival in multiple cohorts of AML patients receiving treatment with the cytidine nucleoside analog cytarabine...
February 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28209594/adolescents-and-young-adults-with-acute-lymphoblastic-leukemia-and-acute-myeloid-leukemia-impact-of-care-at-specialized-cancer-centers-on-survival-outcome
#18
Julie Wolfson, Can-Lan Sun, Laura Wyatt, Wendy Stock, Smita Bhatia
Background: Adolescents and young adults (AYA; 15-39 years) with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) experience inferior survival when compared with children. Impact of care at NCI-designated Comprehensive Cancer Centers (CCC) or Children's Oncology Group sites (COG) on survival disparities remains unstudied.Methods: Using the Los Angeles cancer registry, we identified 1,870 ALL or AML patients between 1 and 39 years at diagnosis. Cox regression analyses assessed risk of mortality; younger age + CCC/COG served as the referent group...
February 16, 2017: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/28208868/female-genital-tract-involvement-in-acute-lymphoblastic-leukemia-a-rare-case-report
#19
Vikram Narang, Amit Dhiman, Bhavna Garg, Neena Sood
Female Genital Tract (FGT) involvement with hematologic neoplasms is uncommon and the hematologic malignancies which involve the female genital organs are usually non-Hodgkin's lymphoma. Involvement of the uterus and cervix with Acute Lymphoblastic Leukaemia (ALL) is extremely rare, and ovarian involvement is even rarer. We report the case of a young lady who presented with tubo-ovarian mass, excessive post-operative bleeding (post-total abdominal hystrerctomy and bilateral salpingo-oophorectomy) and was diagnosed to have ALL with blood and tissue involvement by histopathology and flow cytometry...
December 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28207808/autologous-hematopoietic-stem-cell-transplantation-in-lymphoma-patients-is-associated-with-a-decrease-in-the-double-strand-break-repair-capacity-of-peripheral-blood-lymphocytes
#20
Sandrine Lacoste, Smita Bhatia, Yanjun Chen, Ravi Bhatia, Timothy R O'Connor
Patients who undergo autologous hematopoietic stem cell transplantation (aHCT) for treatment of a relapsed or refractory lymphoma are at risk of developing therapy related- myelodysplasia/acute myeloid leukemia (t-MDS/AML). Part of the risk likely resides in inherent interindividual differences in their DNA repair capacity (DRC), which is thought to influence the effect chemotherapeutic treatments have on the patient's stem cells prior to aHCT. Measuring DRC involves identifying small differences in repair proficiency among individuals...
2017: PloS One
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