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Acute lymphoide leukemia

Maliha Khan, Rabbia Siddiqi, Kiran Naqvi
Mixed phenotype acute leukemia (MPAL) is an uncommon diagnosis, representing only about 2-5% of acute leukemia cases. The blast cells of MPAL express multilineage immunophenotypic markers and may have a shared B/T/myeloid phenotype. Due to historical ambiguity in the diagnosis of MPAL, the genetics and clinical features of this disease remain poorly characterized. Based on the 2008 and 2016 World Health Organization classifications, myeloid lineage is best determined by presence of myeloperoxidase, while B and T lymphoid lineages are demonstrated by CD19 and cytoplasmic CD3 expression...
March 15, 2018: Annals of Hematology
Amanda Przespolewski, Andras Szeles, Eunice S Wang
Evasion of the host immune system is a key mechanism to promote malignant progression. Therapeutically targeting immune pathways has radically changed the treatment paradigm for solid and lymphoid tumors but has yet to be approved for myeloid malignancies. Here, we summarize the most recent advances in immunotherapy for acute myeloid leukemia. Topics reviewed here include adoptive cellular approaches (chimeric antigen receptor-T cells, natural killer and other immune cells), checkpoint inhibitors (anti-PD-1/PD-L1, anti-CTLA-4 and TIM-3) and vaccines (WT-1, HLA-A2 and hTERT)...
March 15, 2018: Future Oncology
Can Chen, Xilian Huang, Kaile Wang, Kuang Chen, Danquan Gao, Shenxian Qian
Acute promyelocytic leukemia (APL) is a rare leukemia characterized by the balanced reciprocal translocation between the promyelocytic leukemia gene on chromosome 15 and the retinoic acid receptor α (RARα) gene on chromosome 17, and accounts for 10-15% of newly diagnosed acute myeloid leukemia each year. The combined use of all-trans retinoic acid and arsenic trioxide (ATO) as primary therapy has markedly improved the survival rate of patients with APL. Mortality in the first 30 days following therapy remains a major contribution to treatment failure...
April 2018: Oncology Letters
Rene Marke, Frank N van Leeuwen, Blanca Scheijen
Transcription factor IKZF1 (IKAROS) acts as a critical regulator of lymphoid differentiation and is frequently deleted or mutated in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). IKZF1 gene defects are associated with inferior treatment outcome in both childhood and adult BCP-ALL and occur in more than 70% of BCR-ABL1 positive and BCR-ABL1-like ALL cases. Over the past few years, much has been learned about the tumor suppressive function of IKZF1 during leukemia development and the molecular pathways that relate to its impact on treatment outcome...
March 8, 2018: Haematologica
Amir Behdad, Pamela Allen, Xinyan Lu, Xiaolong Alan Zhou, Joan Guitart, Qing Chen, Barbara Pro
Patients with PDGFRA-rearranged hematopoietic neoplasms typically present with chronic eosinophilic leukemia and rarely with acute myeloid leukemia or T-lymphoblastic lymphoma. However, mature T-cell lymphoma has not been previously associated with PDGFRA aberrations. We report a patient who presented with simultaneous T-lymphoblastic lymphoma, focal myeloid proliferation, and cutaneous cytotoxic T-cell lymphoma refractory to chemotherapy. The presence of myeloid and lymphoid lineages prompted genetic and molecular studies...
February 21, 2018: American Journal of Dermatopathology
Martin Stanulla, Elif Dagdan, Marketa Zaliova, Anja Möricke, Chiara Palmi, Giovanni Cazzaniga, Cornelia Eckert, Geertruy Te Kronnie, Jean-Pierre Bourquin, Beat Bornhauser, Rolf Koehler, Claus R Bartram, Wolf-Dieter Ludwig, Kirsten Bleckmann, Stefanie Groeneveld-Krentz, Denis Schewe, Stefanie V Junk, Laura Hinze, Norman Klein, Christian P Kratz, Andrea Biondi, Arndt Borkhardt, Andreas Kulozik, Martina U Muckenthaler, Giuseppe Basso, Maria Grazia Valsecchi, Shai Izraeli, Britt-Sabina Petersen, Andre Franke, Petra Dörge, Doris Steinemann, Oskar A Haas, Renate Panzer-Grümayer, Hélène Cavé, Richard S Houlston, Gunnar Cario, Martin Schrappe, Martin Zimmermann
Purpose Somatic deletions that affect the lymphoid transcription factor-coding gene IKZF1 have previously been reported as independently associated with a poor prognosis in pediatric B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). We have now refined the prognostic strength of IKZF1 deletions by analyzing the effect of co-occurring deletions. Patients and Methods The analysis involved 991 patients with BCP ALL treated in the Associazione Italiana Ematologia ed Oncologia Pediatrica-Berlin-Frankfurt-Muenster (AIEOP-BFM) ALL 2000 trial with complete information for copy number alterations of IKZF1, PAX5, ETV6, RB1, BTG1, EBF1, CDKN2A, CDKN2B, Xp22...
March 2, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Charles E de Bock, Sofie Demeyer, Sandrine Degryse, Delphine Verbeke, Bram Sweron, Olga Gielen, Roel Vandepoel, Carmen Vicente, Marlies Vanden Bempt, Antonis Dagklis, Ellen Geerdens, Simon Bornschein, Rik Gijsbers, Jean Soulier, Jules P Meijerink, Merja Heinäniemi, Susanna Teppo, Maria Bouvy-Liivrand, Olli Lohi, Enrico Radaelli, Jan Cools
Leukemia is caused by the accumulation of multiple genomic lesions in hematopoietic precursor cells. However, how these events cooperate during oncogenic transformation remains poorly understood. We studied the cooperation between activated JAK3/STAT5 signaling and HOXA9 overexpression, two events identified as significantly co-occurring in T-cell acute lymphoblastic leukemia. Expression of mutant JAK3 and HOXA9 led to a rapid development of leukemia originating from multipotent or lymphoid-committed progenitors, with a significant decrease in disease latency compared to JAK3 or HOXA9 alone...
March 1, 2018: Cancer Discovery
Kento Umino, Shin-Ichiro Fujiwara, Takashi Ikeda, Yumiko Toda, Shoko Ito, Kiyomi Mashima, Daisuke Minakata, Hirofumi Nakano, Ryoko Yamasaki, Yasufumi Kawasaki, Miyuki Sugimoto, Chihiro Yamamoto, Masahiro Ashizawa, Kaoru Hatano, Kazuya Sato, Iekuni Oh, Ken Ohmine, Kazuo Muroi, Yoshinobu Kanda
OBJECTIVE: Myeloid/lymphoid neoplasms with fibroblast growth factor receptor-1 (FGFR1) rearrangement are hematopoietic stem cell disorders with a poor prognosis, but no established standard therapy. METHODS: We experienced a patient with T-lymphoblastic lymphoma (LBL) associated with FGFR1 rearrangement who underwent cord blood transplantation, but died of pulmonary complication. We collected the clinical data of patients with FGFR1 rearrangement from the medical literature and analyzed 45 patients, including our patient...
February 28, 2018: Hematology (Amsterdam, Netherlands)
Leonidas Benetatos, George Vartholomatos
DNA methylation (CpG methylation) exerts an important role in normal differentiation and proliferation of hematopoietic stem cells and their differentiated progeny, while it has also the ability to regulate myeloid versus lymphoid fate. Mutations of the epigenetic machinery are observed in hematological malignancies including acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) resulting in hyper- or hypo-methylation affecting several different pathways. Enhancers are cis-regulatory elements which promote transcription activation and are characterized by histone marks including H3K27ac and H3K4me1/2...
February 26, 2018: Cellular and Molecular Life Sciences: CMLS
Florence Zylbersztejn, Mario Flores-Violante, Thibault Voeltzel, Franck-Emmanuel Nicolini, Sylvain Lefort, Véronique Maguer-Satta
The microenvironment (niche) governs the fate of stem cells (SC) by balancing self-renewal and differentiation. Increasing evidence indicates that the tumor niche plays an active role in cancer but its (important) properties for tumor initiation progression and resistance remain to be identified. Clinical data show that leukemic stem cells (LSC) survival is responsible for disease persistence and drug resistance probably due to their sustained interactions with the tumor niche. The Bone Morphogenetic Protein (BMP) signaling is a key pathway controlling stem cells and their niche, such as BMP2 and BMP4 important in both normal and cancer context...
February 22, 2018: Experimental Hematology
Carmelo Gurnari, Paola Panetta, Emiliano Fabiani, Anna Maria Nardone, Diana Postorivo, Giulia Falconi, Luca Franceschini, Manuela Rizzo, Vito Mario Rapisarda, Eleonora De Bellis, Francesco Lo-Coco, Maria Teresa Voso
The World Health Organization classifies atypical chronic myeloid leukemia (aCML) as a myeloproliferative/myelodisplastic hematological disorder. The primary manifestations are leukocytosis with disgranulopoiesis, absence of basophilia and/or monocytosis, splenomegaly and absence of Philadelphia chromosome or BCR/ABL fusion. Overall 50-65% of patients demonstrate karyotypic abnormalities, although no specific cytogenetic alterations have been associated with this disease. X chromosome alterations have been rarely reported in myeloid malignancies...
March 2018: Molecular and Clinical Oncology
Lisa Deng, Briana M Richine, Elizabeth L Virts, Victoria N Jideonwo-Auman, Rebecca J Chan, Reuben Kapur
PTPN11 gain-of-function mutation is the most common mutation found in patients with juvenile myelomonocytic leukemia and DNMT3A loss occurs in over 20% of acute myeloid leukemia patients. We studied the combined effect of both Ptpn11 gain-of-function mutation (D61Y) and Dnmt3a haploinsufficiency on mouse hematopoiesis, the presence of which has been described in both juvenile myelomonocytic leukemia and acute myeloid leukemia patients. Double mutant mice rapidly become moribund relative to any of the other genotypes, which is associated with enlargement of the spleen and an increase in white blood cell counts...
January 19, 2018: Oncotarget
Megan Romeo, Tetiana Hutchison, Aditi Malu, Averi White, Janice Kim, Rachel Gardner, Katie Smith, Katherine Nelson, Rachel Bergeson, Ryan McKee, Carolyn Harrod, Lee Ratner, Bernhard Lüscher, Ernest Martinez, Robert Harrod
In normal cells, aberrant oncogene expression leads to the accumulation of cytotoxic metabolites, including reactive oxygen species (ROS), which can cause oxidative DNA-damage and apoptosis as an intrinsic barrier against neoplastic disease. The c-Myc oncoprotein is overexpressed in many lymphoid cancers due to c-myc gene amplification and/or 8q24 chromosomal translocations. Intriguingly, p53 is a downstream target of c-Myc and hematological malignancies, such as adult T-cell leukemia/lymphoma (ATL), frequently contain wildtype p53 and c-Myc overexpression...
February 17, 2018: Virology
Francine Marie Foss, Terri Parker
LESSONS LEARNED: Clofarabine can be active in relapsed and refractory lymphoid malignancies on a weekly dosing schedule.Responses were seen in patients with T-cell lymphomas, including cutaneous T-cell lymphoma, but not in patients with aggressive B-cell lymphomas. BACKGROUND: Clofarabine is a second-generation purine nucleoside analog currently approved for the treatment of pediatric relapsed or refractory acute lymphoblastic leukemia. In adults, clofarabine has been investigated in several phase I and II trials as a single agent and in combination for relapsed or refractory acute leukemia...
February 7, 2018: Oncologist
Fang Ye
T-cell acute lymphoblastic leukemia (T-ALL) is a lymphoid malignancy caused by the oncogenic transformation of immature T-cell progenitors. Many biologically relevant genetic and epigenetic alterations have been identified as driving factors for this transformation. Recently, microRNAs (miRNAs) have been shown to influence various leukemias, including T-ALL. Aberrant expression of miRNAs can function as either oncogenes or tumor suppressors in T-ALL through the regulation of cell migration, invasion, proliferation, apoptosis, and chemoresistance...
January 12, 2018: Oncotarget
Theresa H M Keegan, Lawrence H Kushi, Qian Li, Ann Brunson, X Chawla, Helen K Chew, Marcio Malogolowkin, Ted Wun
PURPOSE: Few population-based studies have focused on cardiovascular disease (CVD) risk in adolescent and young adult (AYA; 15-39 years) cancer survivors and none have considered whether CVD risk differs by sociodemographic factors. METHODS: Analyses focused on 79,176 AYA patients diagnosed with 14 first primary cancers in 1996-2012 and surviving > 2 years after diagnosis with follow-up through 2014. Data were obtained from the California Cancer Registry and State hospital discharge data...
February 9, 2018: Journal of Cancer Survivorship: Research and Practice
Laurie Freire Boullosa, Payalben Savaliya, Stephanie Bonney, Laurence Orchard, Hannah Wickenden, Cindy Lee, Evelien Smits, Alison H Banham, Ken I Mills, Kim Orchard, Barbara-Ann Guinn
B-cell acute lymphoblastic leukemia (B-ALL) is a rare heterogeneous disease characterized by a block in lymphoid differentiation and a rapid clonal expansion of immature, non-functioning B cells. Adult B-ALL patients have a poor prognosis with less than 50% chance of survival after five years and a high relapse rate after allogeneic haematopoietic stem cell transplantation. Novel treatment approaches are required to improve the outcome for patients and the identification of B-ALL specific antigens are essential for the development of targeted immunotherapeutic treatments...
January 9, 2018: Oncotarget
Fan Yang, Houshun Fang, Dan Wang, Yao Chen, Yonggong Zhai, Bin-Bing S Zhou, Hui Li
Acute lymphoblastic leukemia (ALL) is an aggressive hematological tumor resulting from the malignant transformation of lymphoid progenitors. Thiopurine is a widely used drug in the maintaining treatment of ALL. After a period of chemotherapy, 20% of pediatric patients and over 50% of adult patients will relapse. To investigate the mechanisms of drug resistance in vitro , we established the thiopurine resistant cell lines Reh-6MPR (6-MP Resistant cell) and Reh-6TGR (6-TG Resistant cell) by stepwise selection of the ALL cell line Reh...
January 5, 2018: Oncotarget
Rayven Snodgrass, Leonard T Nguyen, Maggie Guo, Marcus Vaska, Christopher Naugler, Fariborz Rashid-Kolvear
OBJECTIVE: Acute lymphocytic leukemia (ALL) is a rare malignant neoplasm that develops from abnormal lymphoid stem cells. ALL incidence is highest among children and declines towards adolescence. There is limited data on the epidemiology of ALL, especially in Canada. This retrospective cohort study used patient data from the Calgary Laboratory Services Cancer Cytogenetics Laboratory to report the incidence rate of ALL in Calgary, Alberta, Canada. New cases of ALL were identified for the 5-year period of January 1, 2011 until December 31, 2015...
February 7, 2018: BMC Research Notes
Ming Zhang, Dongdong Mao, Weina Zhang
B-cell acute lymphoblastic leukemia (B-ALL) is characterized by various fusion genes resulted from chromosome translocations, and MEF2D related fusions are recently identified in a B-ALL subtype with relatively worse survival. In this study, we investigated the pathogenic role of MEF2D-SS18 fusion in B-ALL. The recombinant retrovirus and lentivirus plasmids containing the MEF2D-SS18 transcript were constructed for functional studies. Immuno-fluorescent staining presented the nuclear localization of MEF2D-SS18...
February 2, 2018: Biochemical and Biophysical Research Communications
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