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Acute lymphoide leukemia

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https://www.readbyqxmd.com/read/29346763/derepression-of-the-iroquois-homeodomain-transcription-factor-gene-irx3-confers-differentiation-block-in-acute-leukemia
#1
Tim D D Somerville, Fabrizio Simeoni, John A Chadwick, Emma L Williams, Gary J Spencer, Katalin Boros, Christopher Wirth, Eleni Tholouli, Richard J Byers, Tim C P Somervaille
The Iroquois homeodomain transcription factor gene IRX3 is expressed in the developing nervous system, limb buds, and heart, and transcript levels specify obesity risk in humans. We now report a functional role for IRX3 in human acute leukemia. Although transcript levels are very low in normal human bone marrow cells, high IRX3 expression is found in ∼30% of patients with acute myeloid leukemia (AML), ∼50% with T-acute lymphoblastic leukemia, and ∼20% with B-acute lymphoblastic leukemia, frequently in association with high-level HOXA gene expression...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29330145/mbd2-ablation-impairs-lymphopoiesis-and-impedes-progression-and-maintenance-of-t-all
#2
Mi Zhou, Kuangguo Zhou, Ling Cheng, Xing Chen, Jue Wang, Xiao-Min Wang, Yingchi Zhang, Qilin Yu, Shu Zhang, Di Wang, Liang Huang, Mei Huang, Ding Ma, Tao Cheng, Cong-Yi Wang, Weiping Yuan, Jianfeng Zhou
Aberrant DNA methylation patterns in leukemia might be exploited for therapeutic targeting. In this study, we employed a genetically deficient mouse model to explore the role of the methylated DNA binding protein MBD2 in normal and malignant hematopoiesis. MBD2 ablation led to diminished lymphocytes. Functional defects of the lymphoid compartment were also observed after in vivo reconstitution of MBD2-deficient hematopoietic stem cells (HSC). In an established model of Notch1-driven T cell acute lymphoblastic leukemia (T-ALL), MBD2 ablation impeded malignant progression and maintenance by attenuating the Wnt signaling pathway...
January 12, 2018: Cancer Research
https://www.readbyqxmd.com/read/29330049/the-histone-demethylase-phf8-promotes-adult-acute-lymphoblastic-leukemia-through-interaction-with-the-mek-erk-signaling-pathway
#3
Yue Fu, Yaling Yang, Xiaoming Wang, Xiaolin Yin, Minran Zhou, Siqi Wang, Lin Yang, Tao Huang, Man Xu, Chunyan Chen
Adult acute lymphoblastic leukemia (ALL) is a malignant disorder of lymphoid progenitor cells that is associated with a high risk of relapse and poor prognosis. Thus, novel pathogenic mechanisms and therapeutic targets need to be explored. Histone methylation is one of the most significant chromatin post-translational modifications. Here, we show that the histone demethylase PHF8 is highly expressed in a large number of ALL clinical specimens and that PHF8 expression is associated with ALL progression. PHF8 knockdown inhibits proliferation and promotes the apoptosis of ALL cells in vitro as well as attenuates tumor growth in vivo...
January 9, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29321428/synchronous-occurrence-of-mycosis-fungoides-diffuse-large-b-cell-lymphoma-and-acute-myeloid-leukemia-a-report-of-two-cases
#4
Junichi Miyatake, Hiroaki Inoue, Kentarou Serizawa, Yasuyoshi Morita, J L Espinoza, Hirokazu Tanaka, Takahiro Shimada, Yoichi Tatsumi, Takashi Ashida, Itaru Matsumura
Patients with mycosis fungoides (MF), the most common subtype of primary cutaneous T-cell lymphoma, have an increased risk of developing secondary malignancies. We herein report two rare cases of MF concurring with diffuse large B cell lymphoma (B lymphoid lineage) and acute myeloid leukemia (myeloid lineage) in two otherwise healthy elderly patients. Potential etiologic factors, including the impact of the therapy-associated inflammatory response on the development of secondary tumors in patients with MF, are discussed...
January 11, 2018: Internal Medicine
https://www.readbyqxmd.com/read/29320898/did-i-miss-it-discovering-hidden-coexisting-hematological-neoplasms-a-single-institutional-review-of-100-collision-tumors
#5
Evan Himchak, Etan Marks, Yang Shi, Yanhua Wang
A collision tumor is defined as two histologically distinct tumor types identified at the same anatomic site. Hematolymphoid proliferative disorders (HLPDs), which coincide with non-hematological neoplasms, can mimic an immune response and can easily be overlooked as an immune reaction to a solid organ neoplasm, especially when low grade. In order to avoid a delay in the diagnosis of a HLPD during the workup for a non-hematological neoplasm, we identified a cohort of 100 cases with a HLPD diagnosis during the initial workup and treatment of a non-hematological neoplasm, or vice versa...
January 1, 2018: International Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29312638/coregulator-profiling-of-the-glucocorticoid-receptor-in-lymphoid-malignancies
#6
Dorien Clarisse, Jonathan Thommis, Karlien Van Wesemael, René Houtman, Dariusz Ratman, Jan Tavernier, Fritz Offner, Ilse Beck, Karolien De Bosscher
Coregulators cooperate with nuclear receptors, such as the glucocorticoid receptor (GR), to enhance or repress transcription. These regulatory proteins are implicated in cancer, yet, their role in lymphoid malignancies, including multiple myeloma (MM) and acute lymphoblastic leukemia (ALL), is largely unknown. Here, we report the use and extension of the microarray assay for real-time nuclear receptor coregulator interactions (MARCoNI) technology to detect coregulator associations with endogenous GR in cell lysates...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29305553/preclinical-efficacy-of-daratumumab-in-t-cell-acute-lymphoblastic-leukemia-t-all
#7
Karen L Bride, Tiffaney L Vincent, Soo-Yeon Im, Richard Aplenc, David M Barrett, William L Carroll, Robin Carson, Yunfeng Dai, Meenakshi Devidas, Kimberly P Dunsmore, Tori Fuller, Tina Glisovic-Aplenc, Terzah M Horton, Stephen P Hunger, Mignon L Loh, Shannon L Maude, Elizabeth A Raetz, Stuart S Winter, Stephan A Grupp, Michelle L Hermiston, Brent L Wood, David T Teachey
As a consequence of acquired or intrinsic disease resistance, the prognosis for patients with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) is dismal. Novel, less toxic drugs are clearly needed. One of the most promising emerging therapeutic strategies for cancer treatment is targeted immunotherapy. Immune therapies have improved outcomes for patients with other hematologic malignancies including B-ALL, however no immune therapy has been successfully developed for T-ALL. We hypothesize targeting CD38 will be effective against T-ALL...
January 5, 2018: Blood
https://www.readbyqxmd.com/read/29296886/constitutive-ras-signaling-and-ink4a-arf-inactivation-cooperate-during-the-development-of-b-all-in-mice
#8
Tomasz Sewastianik, Meng Jiang, Kumar Sukhdeo, Sanjay S Patel, Kathryn Roberts, Yue Kang, Ahmad Alduaij, Peter S Dennis, Brian Lawney, Ruiyang Liu, Zeyuan Song, Jessie Xiong, Yunyu Zhang, Madeleine E Lemieux, Geraldine S Pinkus, Jeremy N Rich, David M Weinstock, Charles G Mullighan, Norman E Sharpless, Ruben D Carrasco
Despite recent advances in treatment, human precursor B-cell acute lymphoblastic leukemia (B-ALL) remains a challenging clinical entity. Recent genome-wide studies have uncovered frequent genetic alterations involving RAS pathway mutations and loss of the INK4A/ARF locus, suggesting their important role in the pathogenesis, relapse, and chemotherapy resistance of B-ALL. To better understand the oncogenic mechanisms by which these alterations might promote B-ALL and to develop an in vivo preclinical model of relapsed B-ALL, we engineered mouse strains with induced somatic KrasG12D pathway activation and/or loss of Ink4a/Arf during early stages of B-cell development...
November 28, 2017: Blood Advances
https://www.readbyqxmd.com/read/29290585/a-human-ips-model-implicates-embryonic-b-myeloid-fate-restriction-as-developmental-susceptibility-to-b%C3%A2-acute-lymphoblastic-leukemia-associated-etv6-runx1
#9
Charlotta Böiers, Simon E Richardson, Emma Laycock, Alya Zriwil, Virginia A Turati, John Brown, Jason P Wray, Dapeng Wang, Chela James, Javier Herrero, Ewa Sitnicka, Stefan Karlsson, Andrew J H Smith, Sten Erik W Jacobsen, Tariq Enver
ETV6-RUNX1 is associated with childhood acute B-lymphoblastic leukemia (cALL) functioning as a first-hit mutation that initiates a clinically silent pre-leukemia in utero. Because lineage commitment hierarchies differ between embryo and adult, and the impact of oncogenes is cell-context dependent, we hypothesized that the childhood affiliation of ETV6-RUNX1 cALL reflects its origins in a progenitor unique to embryonic life. We characterize the first emerging B cells in first-trimester human embryos, identifying a developmentally restricted CD19-IL-7R+ progenitor compartment, which transitions from a myeloid to lymphoid program during ontogeny...
December 27, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29286525/the-incidence-of-hematological-neoplasms-morbidity-on-radiation-contaminated-territories-in-cherkasy-region
#10
V V Paramonov
OBJECTIVE: The main goal was to analyze the incidence of the morbidity in 1980, 1989, 2001, 2014 years and the structures of the absolute number of hematopoietic and lymphoid neoplasms cases during the period 1980-2014 on radiation contaminated and not contaminated territories in Cherkasy region. MATERIALS AND METHODS: The epidemiological indecies of hematological neoplasms were analyzed on radiation con taminated and not contaminated territories in Cherkasy region during the period from 1980 to 2014...
December 2017: Problemy Radiat︠s︡iĭnoï Medyt︠s︡yny Ta Radiobiolohiï
https://www.readbyqxmd.com/read/29200701/a-rare-extramedullary-and-extralymphoid-presentation-of-mixed-phenotypic-blastic-hematolymphoid-neoplasm-a-study-of-two-cases
#11
Kiran Ghodke, Prashant Tembhare, Nikhil Patkar, P G Subramanian, Brijesh Arora, Sumeet Gujral
Mixed phenotype acute leukemia (MPAL) is a rare hematolymphoid neoplasm, representing only 3%-5% of acute leukemia. Although MPAL has been sufficiently described in the literature, its extramedullary presentation as a solitary lesion without leukemic (bone marrow [BM]) involvement is rarely described. We are presenting two cases of mixed phenotypic blastic hematolymphoid neoplasms without leukemic involvement at disease presentation in 8-year-old female and 21-year-old male patients. Both the cases had extralymphatic bone involvement in the form of solitary bone lesion...
July 2017: Indian Journal of Medical and Paediatric Oncology
https://www.readbyqxmd.com/read/29197675/homozygous-hla-c1-is-associated-with-reduced-risk-of-relapse-after-hla-matched-transplantation-in-patients-with-myeloid-leukemia
#12
Nobuyoshi Arima, Junya Kanda, Junji Tanaka, Toshio Yabe, Yasuo Morishima, Sung-Won Kim, Yuho Najima, Yukiyasu Ozawa, Tetsuya Eto, Heiwa Kanamori, Takehiko Mori, Naoki Kobayashi, Tadakazu Kondo, Hirohisa Nakamae, Naoyuki Uchida, Masami Inoue, Takahiro Fukuda, Tatsuo Ichinohe, Yoshiko Atsuta, Yoshinobu Kanda
Natural killer (NK) cells assume graft-versus-leukemia alloreactivity after hematopoietic stem cell transplantation (HSCT) through their inhibitory killer cell immunoglobulin-like receptors (KIRs). KIR2D family members recognize HLA-C alleles with Asn80 (HLA-C1) or Lys80 (HLA-C2). The predominance of HLA-C1 over HLA-C2 and the frequent presence of KIR2DL1 are characteristic of Japanese people. We compared clinical outcomes among homozygous HLA-C1 (HLA-C1/C1) patients and heterozygous HLA-C1/C2 patients who underwent HLA-matched HSCT for hematologic malignancies by assessing the data of 10,638 patients from the Japanese national registry...
December 27, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29196889/durable-resolution-of-severe-psoriasis-in-a-patient-treated-with-pentostatin-for-hairy-cell-leukemia-a-case-report
#13
Tamim Alsuliman, Kaiss Lassoued, Maifa Belghoul, Karima Debbache, Bachra Choufi
INTRODUCTION: Pentostatin (2'-deoxycoformycin) and cladribine (2-chlorodeoxyadenosine) are adenosine analogues widely used to treat lymphoid malignancies, mainly hairy cell leukemia (HCL). Oral or parenteral adenosine analogues have been also used as immunomodulatory agents in multiple sclerosis and in acute graft-versus-host disease. CASE REPORT: Here, we report the case of a 43-year-old patient with a history of extensive psoriasis who later developed HCL. RESULTS: The patient had achieved complete remission of both psoriasis and HCL after receiving intravenous infusions of pentostatin...
December 1, 2017: Dermatology and Therapy
https://www.readbyqxmd.com/read/29177615/etv6-abl1-fusion-combined-with-monosomy-7-in-childhood-b-precursor-acute-lymphoblastic-leukemia
#14
Suguru Uemura, Noriyuki Nishimura, Daiichiro Hasegawa, Akemi Shono, Kimiyoshi Sakaguchi, Hisayuki Matsumoto, Yuji Nakamachi, Jun Saegusa, Takehito Yokoi, Teppei Tahara, Akihiro Tamura, Nobuyuki Yamamoto, Atsuro Saito, Aiko Kozaki, Kenji Kishimoto, Toshiaki Ishida, Nanako Nino, Satoru Takafuji, Takeshi Mori, Kazumoto Iijima, Yoshiyuki Kosaka
ETV6-ABL1 fusion is a rare but recurrent oncogenic lesion found in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL), without an established chromosomal abnormality, and is associated with poor outcome. In ETV6-ABL1-positive cases, an in-frame fusion produced by a complex rearrangement results in constitutive chimeric tyrosine kinase activity. Monosomy 7 is also a rare and unfavorable chromosomal abnormality in childhood BCP-ALL. Here, we report a 14-year-old female BCP-ALL patient with ETV6-ABL1 fusion combined with monosomy 7...
November 24, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29175473/mechanisms-underlying-the-heterogeneity-of-myelodysplastic-syndromes
#15
REVIEW
Charles Dussiau, Michaela Fontenay
Myelodysplastic syndromes (MDS) are hematopoietic stem cell (HSC) disorders in which recurrent chromosome abnormalities and gene mutations define a clonal hematopoiesis. The MDS-initiating cell is a rare HSC which transmits the genetic abnormalities to its myeloid and lymphoid progeny. The heterogeneity of MDS phenotypes could be linked to the diversity of genetic events involving epigenetic regulators, chromatin modifiers, splicing factors, transcription factors and signaling adaptors, the various combinations and order of mutations in cooperating genes, and the variegation of clonal hematopoietic hierarchy...
November 22, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/29171939/initial-flow-cytometric-evaluation-of-the-clearllab-lymphoid-screen
#16
B D Hedley, G Cheng, J Luider, W Kern, G Lozanski, I Chin-Yee, L E Lowes, M Keeney, D Careaga, R Magari, L Tejidor
INTRODUCTION: Flow cytometric immunophenotyping (FCI) is an integral part in the diagnosis and classification of hematologic malignancies. FCI results also influence therapeutic decisions and disease prognosis. ClearLLab LS is a 12-antibody 10-color cocktail provided in dry format designed as a screen for patients suspected of having hematolymphoid disease. METHODS: A blinded comparison between ClearLLab LS, (CD8-FITC,Kappa-FITC,CD4-PE,Lambda-PE,CD19-ECD,CD56-PE-Cy5...
November 24, 2017: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/29165768/recent-perspectives-of-pediatric-leukemia-an-update
#17
Q An, C-H Fan, S-M Xu
Leukemia is defined as an aberrant hyper-proliferation of immature blood cells that do not form solid tumor masses (i.e., liquid cancer). Usually, leukemia could be either of the myeloid or lymphoid lineages, and is classified as acute or chronic in nature. Chronic leukemias tend to have more mature cells and are rare in pediatric patients. Acute leukemias, on the other hand, are typically less mature and commonly occur in patients of all ages and are potentially rapidly fatal if not readily treated. The acute lymphoblastic leukemia (ALL) is the most common childhood malignancy...
October 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29154447/roles-and-clinical-implications-of-micrornas-in-acute-lymphoblastic-leukemia
#18
REVIEW
Simona Ultimo, Alberto M Martelli, Giorgio Zauli, Marco Vitale, George A Calin, Luca M Neri
MicroRNAs (miRNAs) are a class of small noncoding RNAs which regulate the expression of target genes by binding to messenger RNAs. miRNAs play a role in various biological processes, including proliferation, apoptosis and tumorigenesis. Dysregulation of miRNAs is implicated in invasion and metastasis in several human cancer types, and leukemia is not an exception. Acute Lymphoblastic Leukemia (ALL) is an hematological malignancy characterized by the proliferation of early lymphoid precursors that replace normal hematopoietic cells of the bone marrow...
November 20, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29150106/reactions-related-to-asparaginase-infusion-in-a-10-year-retrospective-cohort
#19
Amanda Cabral Dos Santos, Marcelo Gerardin Poirot Land, Nathalia Peroni da Silva, Kelly Oliveira Santos, Elisangela da Costa Lima-Dellamora
INTRODUCTION: Although it is an essential component of the treatment of acute lymphoid leukemia in children, asparaginase causes adverse reactions that sometimes make it impossible to use it fully. Hypersensitivity reactions are the most frequent and may lead to early discontinuation of treatment. The present study aimed to investigate suspicions of adverse reactions during the infusion of asparaginase in a pediatric cohort. METHODS: A retrospective observational study was carried out at a university pediatric institute in the state of Rio de Janeiro...
October 2017: Revista Brasileira de Hematologia e Hemoterapia
https://www.readbyqxmd.com/read/29149251/parental-age-and-risk-of-lymphoid-neoplasms
#20
Gunnar Larfors, Ingrid Glimelius, Sandra Eloranta, Karin E Smedby
High parental age at childbirth has repeatedly been linked to childhood malignancies, while few studies have focused on the offspring's risk of adult cancer. In this population-based case-control study, we identified 32,000 patients with lymphoid neoplasms, diagnosed at ages 0-79 years during the period 1987-2011, and 160,000 matched controls in Sweden. Using prospectively registered data on their first-degree relatives, we evaluated the impact of parental age on the risk of lymphoid neoplasms by subtype. Overall, each 5-year increment in maternal age was associated with a 3% increase in incidence of offspring lymphoid neoplasms (hazard ratio = 1...
November 15, 2017: American Journal of Epidemiology
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