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Mixed phenotype leukemia

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https://www.readbyqxmd.com/read/27802969/ibrutinib-efficacy-and-tolerability-in-patients-with-relapsed-chronic-lymphocytic-leukemia-following-allogeneic-hct
#1
Christine E Ryan, Bita Sahaf, Aaron C Logan, Susan O'Brien, John C Byrd, Peter Hillmen, Jennifer R Brown, Martin J S Dyer, Anthony R Mato, Michael J Keating, Samantha Jaglowski, Fong Clow, Andrew R Rezvani, Lori Styles, Steven E Coutre, David B Miklos
Ibrutinib, a potent and irreversible small molecule inhibitor of both Bruton's tyrosine kinase (BTK) and interleukin-2 inducible kinase (ITK), has been used to treat relapsed/refractory chronic lymphocytic leukemia (CLL) with prolongation of progression-free and overall survival. Here we present 27 patients with relapsed CLL following allogeneic hematopoietic cell transplantation who subsequently received ibrutinib salvage therapy. Sixteen of these patients were part of multi-institutional clinical trials and achieved an overall response rate of 87...
November 1, 2016: Blood
https://www.readbyqxmd.com/read/27798768/network-based-expression-analysis-reveals-key-genes-related-to-glucocorticoid-resistance-in-infant-acute-lymphoblastic-leukemia
#2
Zaynab Mousavian, Abbas Nowzari-Dalini, Ronald W Stam, Yasir Rahmatallah, Ali Masoudi-Nejad
PURPOSE: Despite vast improvements that have been made in the treatment of children with acute lymphoblastic leukemia (ALL), the majority of infant ALL patients (~80 %, < 1 year of age) that carry a chromosomal translocation involving the mixed lineage leukemia (MLL) gene shows a poor response to chemotherapeutic drugs, especially glucocorticoids (GCs), which are essential components of all current treatment regimens. Although addressed in several studies, the mechanism(s) underlying this phenomenon have remained largely unknown...
October 31, 2016: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/27774846/mll-rearranged-mixed-phenotype-acute-leukemia-masquerading-as-b-cell-all
#3
Wei Yang, Phu Tran, Ziad Khan, Sherif Rezk, Susan O'Brien
No abstract text is available yet for this article.
October 24, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27673440/buparlisib-a-pi3k-inhibitor-demonstrates-acceptable-tolerability-and-preliminary-activity-in-a-phase-i-trial-of-patients-with-advanced-leukemias
#4
Brittany Knick Ragon, Hagop Kantarjian, Elias Jabbour, Farhad Ravandi, Jorge Cortes, Gautam Borthakur, LaKiesha DeBose, Zhihong Zeng, Heather Schneider, Naveen Pemmaraju, Guillermo Garcia-Manero, Steven Kornblau, William Wierda, Jan Burger, Courtney D DiNardo, Michael Andreeff, Marina Konopleva, Naval Daver
Phosphatidylinositol-3-kinase (PI3K) signaling plays a crucial role in oncogene-mediated tumor growth and proliferation. Buparlisib (BKM120) is an oral pan-class I PI3K inhibitor. This phase I study was conducted to determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of BKM120 in patients (pts) with relapsed/refractory acute leukemias. Fourteen pts (12 acute myeloid leukemia, 1 acute lymphoblastic leukemia, 1 mixed phenotype leukemia) were enrolled. Twelve pts received BKM-120 80 mg/day and two 100 mg/day...
September 27, 2016: American Journal of Hematology
https://www.readbyqxmd.com/read/27641306/dna-damage-induced-hspc-malfunction-depends-on-ros-accumulation-downstream-of-ifn-1-signaling-and-bid-mobilization
#5
Alpaslan Tasdogan, Suresh Kumar, Gabriele Allies, Julia Bausinger, Franziska Beckel, Helmut Hofemeister, Medhanie Mulaw, Vikas Madan, Karin Scharfetter-Kochanek, Michaela Feuring-Buske, Konstanze Doehner, Günter Speit, A Francis Stewart, Hans Joerg Fehling
Mouse mutants with an impaired DNA damage response frequently exhibit a set of remarkably similar defects in the HSPC compartment that are of largely unknown molecular basis. Using Mixed-Lineage-Leukemia-5 (Mll5)-deficient mice as prototypical examples, we have identified a mechanistic pathway linking DNA damage and HSPC malfunction. We show that Mll5 deficiency results in accumulation of DNA damage and reactive oxygen species (ROS) in HSPCs. Reduction of ROS efficiently reverses hematopoietic defects, establishing ROS as a major cause of impaired HSPC function...
September 7, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/27607436/mixed-phenotype-acute-leukemia-with-t-12-17-p13-q21-taf15-znf384-and-other-chromosome-abnormalities
#6
Katsuya Yamamoto, Shinichiro Kawamoto, Yu Mizutani, Kimikazu Yakushijin, Tomoe Yamashita, Yuji Nakamachi, Seiji Kawano, Yoshitake Hayashi, Hiroshi Matsuoka, Hironobu Minami
The t(12;17)(p13;q11∼21) translocation is a very rare but recurrent cytogenetic aberration observed predominantly in early pre-B acute lymphoblastic leukemia (ALL) with CD19+CD10-CD33+ phenotype. This translocation was shown to form a fusion gene between TAF15 at 17q12 and ZNF384 at 12p13. On the other hand, der(1;18)(q10;q10) has been detected as a rare unbalanced whole-arm translocation leading to trisomy 1q in myeloid malignancies. We describe here the first case of mixed phenotype acute leukemia (MPAL) with a t(12;17)(p13;q21)/TAF15-ZNF384, which also had der(1;18)(q10;q10) as an additional abnormality...
September 9, 2016: Cytogenetic and Genome Research
https://www.readbyqxmd.com/read/27577674/successful-acute-lymphoblastic-leukemia-type-therapy-in-two-children-with-mixed-phenotype-acute-leukemia
#7
Keisuke Otsubo, Miharu Yabe, Hiromasa Yabe, Akiko Fukumura, Tsuyoshi Morimoto, Masahiko Kato, Hiroyuki Mochizuki
Mixed-phenotype acute leukemia (MPAL) is a rare type of leukemia expressing both myeloid and lymphoid markers. There is limited information, especially on pediatric cases. Therefore, the optimal therapeutic approach to pediatric MPAL has not been defined. Here, we report two pediatric cases of MPAL. According to the 2008 World Health Organization (WHO) classification and European Group for the Immunological Characterization of Leukemias (EGIL) criteria, patient 1 was diagnosed with overt MPAL positive for the myeloid marker myeloperoxidase (MPO), and B-lymphoid markers...
August 31, 2016: Pediatrics International: Official Journal of the Japan Pediatric Society
https://www.readbyqxmd.com/read/27563394/optimization-of-a-fragment-based-screening-hit-toward-potent-dot1l-inhibitors-interacting-in-an-induced-binding-pocket
#8
Clemens Scheufler, Henrik Möbitz, Christoph Gaul, Christian Ragot, Céline Be, César Fernández, Kim S Beyer, Ralph Tiedt, Frédéric Stauffer
Mixed lineage leukemia (MLL) gene rearrangement induces leukemic transformation by ectopic recruitment of disruptor of telomeric silencing 1-like protein (DOT1L), a lysine histone methyltransferase, leading to local hypermethylation of H3K79 and misexpression of genes (including HoxA), which drive the leukemic phenotype. A weak fragment-based screening hit identified by SPR was cocrystallized with DOT1L and optimized using structure-based ligand optimization to yield compound 8 (IC50 = 14 nM). This series of inhibitors is structurally not related to cofactor SAM and is not interacting within the SAM binding pocket but induces a pocket adjacent to the SAM binding site...
August 11, 2016: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27547725/congenital-b-lymphoblastic-leukemia-with-a-cryptic-mll-rearrangement-and-post-treatment-evolution-to-mixed-phenotype-acute-leukemia
#9
Elizabeth Moschiano, Gordana Raca, Cecilia Fu, Paul K Pattengale, Mathew J Oberley
Congenital leukemia is a rare event with a poor prognosis. We report a case of congenital leukemia with a cryptic rearrangement of MLL demonstrable only with RT-PCR. Interestingly, with treatment, the patient showed lineage plasticity of the leukemia with the development of monocytic lineage blasts after presenting with B-cell lineage blasts. This was heralded by the development of a new clonal cytogenetic abnormality. This case highlights the primitive nature of the leukemic cells in congenital leukemia, and emphasizes that RT-PCR for MLL rearrangements may identify a subset of cases which are otherwise negative by karyotyping, FISH, and chromosomal microarrays...
2016: Leukemia Research Reports
https://www.readbyqxmd.com/read/27547214/comparing-analytic-methods-for-longitudinal-gwas-and-a-case-study-evaluating-chemotherapy-course-length-in-pediatric-aml-a-report-from-the-children-s-oncology-group
#10
Marijana Vujkovic, Richard Aplenc, Todd A Alonzo, Alan S Gamis, Yimei Li
Regression analysis is commonly used in genome-wide association studies (GWAS) to test genotype-phenotype associations but restricts the phenotype to a single observation for each individual. There is an increasing need for analytic methods for longitudinally collected phenotype data. Several methods have been proposed to perform longitudinal GWAS for family-based studies but few methods are described for unrelated populations. We compared the performance of three statistical approaches for longitudinal GWAS in unrelated subjectes: (1) principal component-based generalized estimating equations (PC-GEE); (2) principal component-based linear mixed effects model (PC-LMEM); (3) kinship coefficient matrix-based linear mixed effects model (KIN-LMEM), in a study of single-nucleotide polymorphisms (SNPs) on the duration of 4 courses of chemotherapy in 624 unrelated children with de novo acute myeloid leukemia (AML) genotyped on the Illumina 2...
2016: Frontiers in Genetics
https://www.readbyqxmd.com/read/27510666/expression-of-cd71-by-flow-cytometry-in-acute-leukemias-more-often-seen-in-acute-myeloid-leukemia
#11
Amit Pande, Pranav Dorwal, Dharmendra Jain, Neetu Tyagi, Simmi Mehra, Ritesh Sachdev, Vimarsh Raina
BACKGROUND: CD71 is a marker that has been usually used for identifying dysplasia in the erythroid series. We have tried to evaluate the expression of CD71 in various types of acute leukemias. MATERIALS AND METHODS: We studied 48 patients of acute leukemia, of which 25 were acute myeloid leukemia (AML), 13 were precursor B-acute lymphoblastic leukemia (B-ALL), 8 were T-ALL, and 2 were mixed phenotype acute leukemia (T/myeloid) as per the WHO classification. RESULTS: We found that the expression of CD71 was most prevalent in AMLs (84%), followed by T-ALL (50%) and least in B-ALL (30%)...
July 2016: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/27466307/first-case-of-biphenotypic-bilineal-b-myeloid-b-monocytic-mixed-phenotype-acute-leukemia-with-t-9-22-q34-q11-2-bcr-abl1
#12
Hyeong Nyeon Kim, Mina Hur, Hanah Kim, Misuk Ji, Hee-Won Moon, Yeo-Min Yun, Mark Hong Lee
Mixed phenotype acute leukemia (MPAL) includes biphenotypic leukemia, bilineal leukemia, or its combination by the 2008 WHO classification. A few cases of combined biphenotypic/bilineal MPAL have been reported so far; they all had biphenotypic expressions in only one of the two distinct leukemic populations. A 43-year-old female presented with leukocytosis and bicytopenia. Her complete blood counts were: hemoglobin, 6.9 g/dL; white blood cells, 62.8×10(9)/L; and platelets, 83×10(9)/L. Neither lymphadenopathy nor organomegaly was observed...
July 2016: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/27408360/mixed-phenotypic-acute-leukemia-presenting-as-mediastinal-mass-2-cases
#13
Rig Vardhan, Jyoti Kotwal, Prosenjit Ganguli, Rehan Ahmed, Ajay Sharma, Jasjit Singh
Mixed phenotype acute leukemia symbolizes a very small subset of acute leukemia that simply cannot be allocated as lymphoid or myeloid lineage. The 2008 World Health Organisation classification established stringent standard for diagnosis of mixed phenotype acute leukemia, accentuating myeloperoxidase for myeloid lineage, cytoplasmic CD3 for T lineage and CD19 with other B markers for B lineage obligation. Mixed phenotype leukemia is rare and 3-5 % of acute leukmias of all age groups, is associated with poor outcome with overall survival of 18 months...
June 2016: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/27392123/frequency-and-outcome-of-pediatric-acute-lymphoblastic-leukemia-with-znf384-gene-rearrangements-including-a-novel-translocation-resulting-in-an-arid1b-znf384-gene-fusion
#14
Mary Shago, Oussama Abla, Johann Hitzler, Sheila Weitzman, Mohamed Abdelhaleem
BACKGROUND: ZNF384 gene rearrangements with multiple partner genes are recurrent in acute leukemia and are most often associated with a precursor B cell immunophenotype. The overall incidence of this genetic category of leukemia is uncertain. PROCEDURE: Patients with ZNF384 gene rearrangements from a cohort of 240 precursor B cell acute lymphoblastic leukemia (ALL) pediatric patients over a 3.5-year time period were characterized with detailed cytogenetic, FISH, genomic, and clinical analyses...
November 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27321126/the-added-values-of-multiplex-reverse-transcriptase-pcr-followed-by-mutation-screening-in-the-initial-evaluation-of-acute-leukemia
#15
B Kim, Y-U Cho, M-H Bae, S Jang, E-J Seo, H-S Chi, C-J Park
INTRODUCTION: This study investigates the benefits of using multiplex reverse transcriptase-PCR (RT-PCR) in addition to standard karyotyping during the initial evaluation of acute leukemia. METHODS: A total of 1114 consecutive specimens from patients with acute leukemia were tested using a commercial multiplex RT-PCR kit (HemaVision, DNA Diagnostic). NPM1 and CEBPA mutations were selectively tested in acute myeloid leukemia (AML) patients with multiplex RT-PCR negativity...
August 2016: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/27233802/clinical-predictors-of-venetoclax-pharmacokinetics-in-chronic-lymphocytic-leukemia-and-non-hodgkin-s-lymphoma-patients-a-pooled-population-pharmacokinetic-analysis
#16
Aksana K Jones, Kevin J Freise, Suresh K Agarwal, Rod A Humerickhouse, Shekman L Wong, Ahmed Hamed Salem
Venetoclax (ABT-199/GDC-0199) is a selective, potent, first-in-class BCL-2 inhibitor that restores apoptosis in cancer cells and has demonstrated clinical efficacy in a variety of hematological malignancies. The objective of this analysis was to characterize the population pharmacokinetics of venetoclax and identify demographic, pathophysiologic, and treatment factors that influence its pharmacokinetics. Plasma concentration samples from 505 subjects enrolled in 8 clinical studies were analyzed using non-linear mixed-effects modeling...
September 2016: AAPS Journal
https://www.readbyqxmd.com/read/27233483/the-philadelphia-chromosome-in-leukemogenesis
#17
REVIEW
Zhi-Jie Kang, Yu-Fei Liu, Ling-Zhi Xu, Zi-Jie Long, Dan Huang, Ya Yang, Bing Liu, Jiu-Xing Feng, Yu-Jia Pan, Jin-Song Yan, Quentin Liu
The truncated chromosome 22 that results from the reciprocal translocation t(9;22)(q34;q11) is known as the Philadelphia chromosome (Ph) and is a hallmark of chronic myeloid leukemia (CML). In leukemia cells, Ph not only impairs the physiological signaling pathways but also disrupts genomic stability. This aberrant fusion gene encodes the breakpoint cluster region-proto-oncogene tyrosine-protein kinase (BCR-ABL1) oncogenic protein with persistently enhanced tyrosine kinase activity. The kinase activity is responsible for maintaining proliferation, inhibiting differentiation, and conferring resistance to cell death...
2016: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/27208809/mixed-phenotype-acute-leukemia-mpal-exhibits-frequent-mutations-in-dnmt3a-and-activated-signaling-genes
#18
Olive S Eckstein, Linghua Wang, Jyotinder N Punia, Steven M Kornblau, Michael Andreeff, David A Wheeler, Margaret A Goodell, Rachel E Rau
Mixed-phenotype acute leukemia (MPAL) is a heterogeneous group of poor-prognosis leukemias with immunophenotypic features of at least two cell lineages. The full spectrum of genetic mutations in this rare disease has not been elucidated, limiting our understanding of disease pathogenesis and our ability to devise targeted therapeutic strategies. Here, we sought to define the mutational landscape of MPAL by performing whole-exome sequencing on samples from 23 adult and pediatric MPAL patients. We identified frequent mutations of epigenetic modifiers, most notably mutations of DNMT3A, in 33% of adult MPAL patients...
August 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27150875/two-elderly-patients-with-philadelphia-chromosome-positive-mixed-phenotype-acute-leukemia-who-were-successfully-treated-with-dasatinib-and-prednisolone
#19
Hiroyuki Takata, Taichi Ikebe, Hitohiro Sasaki, Yasuhiko Miyazaki, Eiichi Ohtsuka, Yoshio Saburi, Masao Ogata, Kuniaki Shirao
Philadelphia chromosome positive (Ph+) mixed phenotype acute leukemia (MPAL) is a rare type of acute leukemia having both myeloid and lymphoid features for which no optimal treatment has yet been established. We herein describe two elderly Ph+MPAL patients who achieved molecular remission without any serious adverse events by treatment with dasatinib and prednisolone. Although dasatinib induction therapy combined with prednisolone is known to be a highly effective treatment for Ph+ acute lymphoblastic leukemia, its efficacy for Ph+MPAL has not been shown...
2016: Internal Medicine
https://www.readbyqxmd.com/read/27144120/the-formation-of-an-aberrant-pax5-transcript-in-a-patient-with-mixed-phenotype-acute-leukemia-harboring-der-9-t-7-9-q11-2-p13
#20
Jun Amaki, Hiromichi Matsushita, Yuka Kitamura, Ryoko Nagao, Hiromichi Murayama, Minoru Kojima, Kiyoshi Ando
We experienced the case of a 56-year-old male with B-lymphoid/myeloid lineage mixed phenotype acute leukemia (MPAL). A cytogenetic analysis of the patient's bone marrow revealed a complex karyotype, including der(9)t(7;9)(q11.2;p13). We identified an aberrant PAX5 transcript, including the exons 1A to 5 and the contiguous intron 5/6 sequence using the 3' rapid amplification of cDNA ends-polymerase chain reaction method, and confirmed their expression in the leukemic cells. Our case suggests that der(9)t(7;9)(q11...
2016: Leukemia Research Reports
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