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Chronic myeloid leukemia

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https://www.readbyqxmd.com/read/28229399/neurological-complications-of-the-leukemias-across-the-ages
#1
REVIEW
Stephanie Berg, Sucha Nand
PURPOSE OF REVIEW: Acute and chronic leukemias are heterogeneous diseases and can affect any part of the body upon initial discovery. Understanding the sequela of systemic involvement is key for proper diagnosis and treatment. RECENT FINDINGS: Over the decades, new research has emerged regarding neurological complications of the myeloid or lymphoid leukemias. Central nervous system involvement usually confers a poor prognosis and requires emergent treatment. Standard of care still involves systemic therapy, intrathecal administration of chemotherapeutic agents, and cranial radiation...
February 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28224300/nilotinib-first-line-therapy-in-patients-with-philadelphia-chromosome-negative-bcr-abl-positive-chronic-myeloid-leukemia-in-chronic-phase-enest1st-sub-analysis
#2
Andreas Hochhaus, Franҫois-Xavier Mahon, Philipp le Coutre, Ljubomir Petrov, Jeroen J W M Janssen, Nicholas C P Cross, Delphine Rea, Fausto Castagnetti, Andrzej Hellmann, Gianantonio Rosti, Norbert Gattermann, Maria Liz Paciello Coronel, Maria Asuncion Echeveste Gutierrez, Valentin Garcia-Gutierrez, Beatrice Vincenzi, Luca Dezzani, Francis J Giles
PURPOSE: The ENEST1st sub-analysis presents data based on Philadelphia chromosome (Ph) status, i.e., Ph+ and Ph-/BCR-ABL1 + chronic myeloid leukemia. METHODS: Patients received nilotinib 300 mg twice daily, up to 24 months. RESULTS: At screening, 983 patients were identified as Ph+ and 30 patients as Ph-/BCR-ABL + based on cytogenetic and RT-PCR assessment; 76 patients had unknown karyotype (excluded from this sub-analysis). In the Ph-/BCR-ABL1 + subgroup, no additional chromosomal aberrations were reported...
February 21, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28223235/interleukin-32-inflammation-and-cancer
#3
REVIEW
Jin Tae Hong, Dong Ju Son, Chong Kil Lee, Do-Young Yoon, Dong Hun Lee, Mi Hee Park
Interleukin-32 (IL-32) is a novel cytokine involved in inflammation and cancer development. IL-32 gene consists of eight small exons, and IL-32 mRNA has nine alternative spliced isoforms, and was thought to be secreted because it contains an internal signal sequence and lacks a transmembrane region. IL-32 is initially expressed selectively in activated T cells by mitogen and activated NK cells and their expression is strongly augmented by microbes, mitogens, and other cytokines. The IL-32 is induced mainly by pathogens and pro-inflammatory cytokines, but IL-32 is more prominent in immune cells than in non-immune tissues...
February 13, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28222219/longitudinal-follow-up-of-adult-survivors-of-ewing-sarcoma-a-report-from-the-childhood-cancer-survivor-study
#4
Neyssa M Marina, Qi Liu, Sarah S Donaldson, Charles A Sklar, Gregory T Armstrong, Kevin C Oeffinger, Wendy M Leisenring, Jill P Ginsberg, Tara O Henderson, Joseph P Neglia, Marilyn A Stovall, Yutaka Yasui, R Lor Randall, David S Geller, Leslie L Robison, Kirsten K Ness
BACKGROUND: Ewing sarcoma survivors (ESSs) are at increased risk for treatment-related complications. The incidence of treatment-related morbidity and late mortality with aging is unknown. METHODS: This study reports survival probabilities, estimated with the Kaplan-Meier method, and the cumulative incidence of cause-specific mortality and chronic conditions among ESSs in the Childhood Cancer Survivor Study who were treated between 1970 and 1986. Piecewise exponential models were used to estimate relative rates (RRs) and 95% confidence intervals (CIs) for these outcomes...
February 21, 2017: Cancer
https://www.readbyqxmd.com/read/28222016/a-review-of-the-challenge-in-measuring-and-standardizing-bcr-abl1
#5
Shuping Yu, Ming Cui, Xiao He, Rongrong Jing, Huimin Wang
Breakpoint cluster region-Abelson (BCR-ABL1) translocation is the characteristic sign of chronic myeloid leukemia (CML). The quantitation of BCR-ABL1 messenger RNA is requisite for patients with CML, and reverse-transcription real-time quantitative polymerase chain reaction (RQ-PCR) is the method used most extensively in testing laboratories worldwide. Nevertheless, substantial variation in RQ-PCR results from different laboratories makes interlaboratory comparability inconvincible owing to the lack of standardization...
February 21, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28218757/allogeneic-stem-cell-transplantation-for-refractory-acute-myeloid-leukemia-in-pediatric-patients-the-uk-experience
#6
P O'Hare, G Lucchini, M Cummins, P Veys, M Potter, S Lawson, A Vora, R Wynn, A Peniket, K Kirkland, R Pearce, J Perry, P J Amrolia
We report outcomes for 44 children who underwent stem cell transplantation (SCT) for refractory AML in the UK between 2000 and 2012. Median age at SCT was 11.5 years. Twenty-three patients had primary refractory and 21 relapsed refractory AML. Refractory disease was confirmed by cytogenetics/molecular genetics in 24 cases. Median follow-up of the whole cohort is 6.8 years (2.1-14.9 years). Thirty patients (68%) achieved a CR following SCT. Transplant-related mortality at 1 year was 18%. Acute GVHD incidence was 52% (grade ⩾III 19%), chronic 7%...
February 20, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28218567/-allogeneic-hematopoietic-stem-cell-transplantation-in-hungary
#7
Árpád Bátai, Péter Reményi, Marienn Réti, Anikó Barta, László Gopcsa, Lilla Lengyel, Éva Torbágyi, Zoltán Csukly, Éva Karászi, Attila Tordai, Hajnalka Andrikovics, Katalin Balassa, Szabolcs Tasnády, Tamás Masszi
INTRODUCTION AND AIM: The publication summarizes the 2548 stem cell transplantations performed in the period of 1993-2015 in Szent Laszló Hospital, Budapest and provides a detailed discussion of the 425 allogeneic transplantations during 2007-2013. METHOD: The analysis explains the major steps of the evolution of allogeneic stem cell transplantation and compares the results of the unique Hungarian allogeneic center. RESULTS: The significant shift in the transplantation indications from chronic myeloid leukemia to myelodysplastic syndromes and the rising age of the recipients are in line with world wide tendencies...
February 2017: Orvosi Hetilap
https://www.readbyqxmd.com/read/28218239/treatment-free-remission-following-frontline-nilotinib-in-patients-with-chronic-myeloid-leukemia-in-chronic-phase-results-from-the-enestfreedom-study
#8
A Hochhaus, T Masszi, F J Giles, J P Radich, D M Ross, M T G Casares, A Hellmann, J Stentoft, E Conneally, V García-Gutiérrez, N Gattermann, W Wiktor-Jedrzejczak, P D le Coutre, B Martino, S Saussele, H D Menssen, W Deng, N Krunic, V Bedoucha, G Saglio
The single-arm, phase 2 ENESTfreedom trial (ClinicalTrials.gov, NCT01784068) assessed the potential for treatment-free remission (TFR; ie, the ability to maintain a molecular response after stopping therapy) following frontline nilotinib treatment. Patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (CML-CP) with MR(4.5) (BCR-ABL1⩽0.0032% on the International Scale; BCR-ABL1(IS)) and ⩾2 years of frontline nilotinib therapy were enrolled. Patients with sustained deep molecular response during the 1-year nilotinib consolidation phase were eligible to stop treatment and enter the TFR phase...
February 20, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28218227/p190-bcr-abl-chronic-myeloid-leukemia-following-a-course-of-s-1-plus-oxaliplatin-therapy-for-advanced-gastric-adenocarcinoma
#9
Hua Wang, Zhi-Yong Wang, Chun-Hong Xin, Ying-Hui Shang, Rui Jing, Fa-Hong Yan, Si-Zhou Feng
No abstract text is available yet for this article.
2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28212528/the-crispr-cas9%C3%A2-system-efficiently-reverts-the-tumorigenic-ability-of-bcr-abl-in-vitro-and-in-a-xenograft-model-of-chronic-myeloid-leukemia
#10
Ignacio García-Tuñón, María Hernández-Sánchez, José Luis Ordoñez, Veronica Alonso-Pérez, Miguel Álamo-Quijada, Rocio Benito, Carmen Guerrero, Jesús María Hernández-Rivas, Manuel Sánchez-Martín
CRISPR/Cas9 technology was used to abrogate p210 oncoprotein expression in the Boff-p210 cell line, a pro-B line derived from interlukin-3-dependent Baf/3, that shows IL-3-independence arising from the constitutive expression of BCR-ABL p210. Using this approach, pools of Boff-p210-edited cells and single edited cell-derived clones were obtained and functionally studied in vitro. The loss of p210 expression in Boff-p210 cells resulted in the loss of ability to grow in the absence of IL-3, as the Baf/3 parental line, showing significantly increased apoptosis levels...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28209720/acquired-expression-of-cbl-q367p-in-mice-induces-dysplastic-myelopoiesis-mimicking-chronic-myelomonocytic-leukemia
#11
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/28207569/poly-adp-ribose-polymerase-inhibition-suppresses-cisplatin-toxicity-in-chronic-myeloid-leukemia-cells
#12
Ling-Yi Xiao, Wai-Ming Kan
Cancer cells may acquire drug resistance by activating DNA repair signaling. Poly ADP-ribose polymerase (PARP) plays an important role in DNA repair and it is overexpressed in many cancers including chronic myeloid leukemia (CML). PARP inhibitors have been used either alone or with other drugs to augment cancer cell death. However, whether PARP inhibitors may also augment cell death induced by chemotherapeutic agents in CML cells has not been studied. K562 cells with or without PARP-1 knockdown were treated with cisplatin alone or together with olaparib...
March 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28205462/atypical-chronic-myeloid-leukemia-in-a-german-shepherd-dog
#13
Christina L Marino, Jimmy N S N Tran, Tracy Stokol
A 4-y-old neutered male German Shepherd Dog was presented with a 3-d duration of lethargy, restlessness, and vomiting. Physical examination revealed generalized lymphadenopathy, pale mucous membranes, systolic heart murmur, dehydration, and fever. Hematologic abnormalities included moderate-to-marked leukocytosis, characterized by neutrophilia with a left shift to progranulocytes and 2% presumptive myeloid blasts, marked anemia that was nonregenerative, and marked thrombocytopenia. Dysplasia was evident in neutrophils and platelets...
February 1, 2017: Journal of Veterinary Diagnostic Investigation
https://www.readbyqxmd.com/read/28194061/performance-of-sokal-and-eutos-scores-for-predicting-cytogenetic-and-molecular-response-in-newly-diagnosed-chronic-myeloid-leukemia-chronic-phase-patients-on-imatinib
#14
Sandip Ganguly, K C Lakshmaiah, Linu Abraham Jacob, Suresh Babu, Lokanatha Dasappa, K S Govind Babu
Sokal index was developed in the pre-imatinib era to predict and prognosticate the outcome of Chronic myeloid leukemia (CML) patients. In the Imatinib era, a new scoring system called EUTOS scoring system has been validated as a predictive marker in CML. The scores have shown variable correlation with complete cytogenetic response (CCyR) and major molecular response (MMR). To assess the performance of Sokal score and EUTOS score as a predictive marker for CCyR and MMR for newly diagnosed CML-CP patients treated with TKIs...
March 2017: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/28192602/smokers-with-chronic-myeloid-leukemia-are-at-a-higher-risk-of-disease-progression-and-premature-death
#15
Michael Lauseker, Joerg Hasford, Susanne Saussele, Stephan Kremers, Doris Kraemer, Walter Lindemann, Rüdiger Hehlmann, Markus Pfirrmann
BACKGROUND: Smoking is suspected to not only be a risk factor for chronic myeloid leukemia but an adverse prognostic factor for the disease as well. The objective of the current study was to investigate the impact of smoking on survival and progression to advanced phases of disease. METHODS: Based on the data of the German CML Study IV, the authors analyzed the effect of smoking using a multivariate Cox model with the addition of the European Treatment and Outcome Study (EUTOS) long-term survival score variables of age, spleen size, thrombocytes, and peripheral blasts as well as sex, comorbidities, and type of treatment center...
February 13, 2017: Cancer
https://www.readbyqxmd.com/read/28192408/macrophages-confer-survival-signals-via-ccr1-dependent-translational-mcl-1-induction-in-chronic-lymphocytic-leukemia
#16
M H A van Attekum, S Terpstra, E Slinger, M von Lindern, P D Moerland, A Jongejan, A P Kater, E Eldering
Protective interactions with bystander cells in micro-environmental niches, such as lymph nodes (LNs), contribute to survival and therapy resistance of chronic lymphocytic leukemia (CLL) cells. This is caused by a shift in expression of B-cell lymphoma 2 (BCL-2) family members. Pro-survival proteins B-cell lymphoma-extra large (BCL-XL), BCL-2-related protein A1 (BFL-1) and myeloid leukemia cell differentiation protein 1 (MCL-1) are upregulated by LN-residing T cells through CD40L interaction, presumably via nuclear factor (NF)-κB signaling...
February 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28191803/population-pharmacokinetics-of-imatinib-and-its-application-to-the-therapeutic-drug-monitoring-middle-east-cml-population
#17
Mehdi Ansari, Behjat Kalantary-Khandani, Abbas Pardakhty, Moein Safavi, Nabi Mosavi, Ehsan Mohajeri
INTRODUCTION: Despite the outstanding results generally obtained with Imatinib in the treatment of chronic myeloid leukemia, some patients show sub-optimal or no response. To evaluate the relationship between steady-state through plasma concentration and clinical response in CML patients. The objectives of this study were to assess the variability in Imatinib pharmacokinetics and to explore the effects of several demographic and biological covariates on the disposition of Imatinib. METHODS: A population pharmacokinetic analysis was performed on 170 plasma samples from 74 adult Iranian chronic myeloid leukemia patients...
September 2016: Gulf Journal of Oncology
https://www.readbyqxmd.com/read/28191543/the-third-time-chronic-myeloid-leukemia-in-lymphoblastic-crisis-with-abl1-kinase-mutation-induced-by-decitabine-dexamethason-combined-with-nilotinib-and-dasatinib
#18
Suli Wang, Chun Qiao, Yu Zhu, Wenyi Shen, Guangsheng He, Jianyong Li
Blast crisis (BC) is the major remaining challenge in the management of chronic myeloid leukemia (CML). The prognosis of the BC patient who carries ABL kinase mutation is very poor. One patient, with lymphoid CML-BC third time, was detected with T315A/F359I/M244V compound mutation by direct sequencing after treatment with tyrosine kinase inhibitions three years. The patient was treated with decitabine, dexamethasone, in combination with nilotinib and dasatinib. Then this patient received a complete hematologic response and cytogenetic response after two cycles of treatment...
December 1, 2016: Journal of Translational Internal Medicine
https://www.readbyqxmd.com/read/28186983/differentiation-status-of-primary-chronic-myeloid-leukemia-cells-affects-sensitivity-to-bcr-abl1-inhibitors
#19
Paavo O Pietarinen, Christopher A Eide, Pilar Ayuda-Durán, Swapnil Potdar, Heikki Kuusanmäki, Emma I Andersson, John P Mpindi, Tea Pemovska, Mika Kontro, Caroline A Heckman, Olli Kallioniemi, Krister Wennerberg, Henrik Hjorth-Hansen, Brian J Druker, Jorrit M Enserink, Jeffrey W Tyner, Satu Mustjoki, Kimmo Porkka
Tyrosine kinase inhibitors (TKI) are the mainstay treatment of BCR-ABL1-positive leukemia and virtually all patients with chronic myeloid leukemia in chronic phase (CP CML) respond to TKI therapy. However, there is limited information on the cellular mechanisms of response and particularly on the effect of cell differentiation state to TKI sensitivity in vivo and ex vivo/in vitro. We used multiple, independent high-throughput drug sensitivity and resistance testing platforms that collectively evaluated 295 oncology compounds to characterize ex vivo drug response profiles of primary cells freshly collected from newly-diagnosed patients with BCR-ABL1-positive leukemia (n = 40) and healthy controls (n = 12)...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28186602/-analysis-of-isodicentric-ph-chromosomes-in-chronic-myeloid-leukemia-blast-crisis
#20
Qian Li, Xiaoji Lin, Ying Lin, Rongxin Yao, Wu Huang, Handong Mei, Jian Gong, Hui Chen, Ningyan Teng
OBJECTIVE: To explore the genetic and clinical characteristics of isodicentric Ph chromosomes [idic(Ph)] in lymphoid blast crisis of chronic myeloid leukemia (CML-BLC). METHODS: Bone marrow aspirates of 2 patients with CML-BLC were analyzed by R banding after 24 hours of culturing. Genomic copy number variations (CNV) were analyzed by single nucleotide polymorphism array (SNP array) in case 1. The results were confirmed with fluorescence in situ hybridization (FISH)...
February 10, 2017: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
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