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https://www.readbyqxmd.com/read/29296896/maintenance-of-telomere-length-in-aml
#1
REVIEW
Peter M Lansdorp
The importance of telomere length to human health, aging, and cancer continues to be underappreciated. This review examines some basics of telomere biology and relates how telomere function, telomerase activity, and mutations in TERC or TERT are involved in bone marrow failure, leukemias, and other cancers. Given the challenge to obtain accurate data on telomerase activity and telomere length in specific cell types, the situation in acute myeloid leukemia (AML) remains puzzling. In most cancers, telomerase levels are increased after cells have encountered a "telomere crisis," which is typically associated with poor prognosis...
November 28, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296778/asxl1-and-bim-germ-line-variants-predict-response-and-identify-cml-patients-with-the-greatest-risk-of-imatinib-failure
#2
Justine E Marum, David T Yeung, Leanne Purins, John Reynolds, Wendy T Parker, Doris Stangl, Paul P S Wang, David J Price, Jonathan Tuke, Andreas W Schreiber, Hamish S Scott, Timothy P Hughes, Susan Branford
Scoring systems used at diagnosis of chronic myeloid leukemia (CML), such as Sokal risk, provide important response prediction for patients treated with imatinib. However, the sensitivity and specificity of scoring systems could be enhanced for improved identification of patients with the highest risk. We aimed to identify genomic predictive biomarkers of imatinib response at diagnosis to aid selection of first-line therapy. Targeted amplicon sequencing was performed to determine the germ line variant profile in 517 and 79 patients treated with first-line imatinib and nilotinib, respectively...
August 8, 2017: Blood Advances
https://www.readbyqxmd.com/read/29231259/pernio-as-the-presenting-sign-of-blast-crisis-in-acute-lymphoblastic-leukemia
#3
Kelly K Park, Bailey Tayebi, Lily Uihlein, Jodi Speiser, Adnan Mir, Pedram Gerami, Anthony Mancini, Wendy Kim
A previously healthy 5-year-old girl presented with acute onset of blue toes and red spots on the nose and fingers. The striking nature of these lesions, along with the finding of submandibular lymphadenopathy, prompted further evaluation. Laboratory findings were remarkable for anemia, high transaminase levels, and high blast count. Histopathologic findings were consistent with early pernio. Further examination revealed acute B-cell lymphoblastic leukemia. Treatment of the leukemia led to resolution of the pernio...
December 12, 2017: Pediatric Dermatology
https://www.readbyqxmd.com/read/29228732/hoxa9-and-hoxa10-induce-cml-myeloid-blast-crisis-development-through-activation-of-myb-expression
#4
Vijay Negi, Bandana A Vishwakarma, Su Chu, Kevin Oakley, Yufen Han, Ravi Bhatia, Yang Du
Mechanisms underlying the progression of Chronic Myeloid Leukemia (CML) from chronic phase to myeloid blast crisis are poorly understood. Our previous studies have suggested that overexpression of SETBP1 can drive this progression by conferring unlimited self-renewal capability to granulocyte macrophage progenitors (GMPs). Here we show that overexpression of Hoxa9 or Hoxa10, both transcriptional targets of Setbp1, is also sufficient to induce self-renewal of primary myeloid progenitors, causing their immortalization in culture...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29179634/azacytidine-in-combination-with-tyrosine-kinase-inhibitors-induced-durable-responses-in-patients-with-advanced-phase-chronic-myelogenous-leukemia
#5
Mathilde Ruggiu, Florence Oberkampf, David Ghez, Pascale Cony-Makhoul, Florence Beckeriche, Isabelle Cano, Anne L Taksin, Omar Benbrahim, Stéphanie Ghez, Hassan Farhat, Sophie Rigaudeau, Noémie de Gunzburg, Diane Lara, Christine Terre, Victoria Raggueneau, Isabel Garcia, Marc Spentchian, Stéphane De Botton, Philippe Rousselot
Although the tyrosine kinase inhibitor (TKI) era has brought great improvement in outcome in chronic myelogenous leukemia (CML), prognosis of accelerated phase or myeloid blast crisis patients or of de novo Philadelphia chromosome-positive acute myeloid leukemia remains poor. We conducted a retrospective study on patients with advanced phase disease treated with a TKI and azacytidine. Sixteen patients were eligible. Median age was 64.9 years, the median number of previous therapies was 2.5 lines, and median follow-up was 23...
November 28, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29151902/coexistence-of-p210bcr-abl-and-cbf%C3%AE-myh11-fusion-genes-in-myeloid-leukemia-a-report-of-4-cases
#6
Yuan-Yuan Wang, Wen-Jing Ding, Feng Jiang, Zi-Xing Chen, Jian-Nong Cen, Xiao-Fei Qi, Jian-Ying Liang, Dan-Dan Liu, Jin-Lan Pan, Su-Ning Chen
Numerous acquired molecular and cytogenetic abnormalities are strongly associated with hematological malignancies. The breakpoint cluster region-ABL proto-oncogene 1 (BCR-ABL) rearrangement leads to a p210 chimeric protein in typical chronic myeloid leukemia (CML), whereas 17-25% of patients with acute lymphocytic leukemia and 0.9-3% patients with de novo acute myeloid leukemia (AML) carry a p190BCR-ABL fusion protein. Cases of patients with AML/CML carrying two specific primary molecular changes, BCR-ABL and core binding factor-β-myosin heavy chain 11 (CBFβ-MYH11) fusion genes have been rarely reported...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29144072/relapse-and-cytogenetic-evolution-in-myeloid-neoplasms
#7
Natalie Ertz-Archambault, Katalin Kelemen
Based on the current WHO Classification of Myeloid Neoplasms, cytogenetic findings play a central role in the diagnostic classification of the myeloid malignancies. Cytogenetic abnormalities detected at primary diagnosis may change over time. Karyotype changes can be characterized as cytogenetic evolution, cytogenetic regression or a combination of both. While the exact mechanism of cytogenetic evolution is not completely understood, the process of cytogenetic evolution is not random, but follows different, and often disease-specific patterns during progression and relapse of myeloid neoplasms...
December 2017: Panminerva Medica
https://www.readbyqxmd.com/read/29123930/chronic-myeloid-leukemia-with-an-e6a2-bcr-abl1-fusion-transcript-cooperating-mutations-at-blast-crisis-and-molecular-monitoring
#8
Mireille Crampe, Karl Haslam, Emma Groarke, Eileen Kelleher, Derville O'Shea, Eibhlin Conneally, Stephen E Langabeer
A minority of chronic myeloid leukemia patients (CML) express a variety of atypical BCR-ABL1 fusion variants and, of these, the e6a2 BCR-ABL1 fusion is generally associated with an aggressive disease course. Progression of CML to blast crisis is associated with acquisition of additional somatic mutations yet these events have not been elucidated in patients with the e6a2 BCR-ABL1 genotype. Moreover, molecular monitoring is only sporadically performed in CML patients with atypical BCR-ABL1 fusion transcripts due to lack of consensus approaches or standardization...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/29076005/nilotinib-vs-imatinib-in-japanese-patients-with-newly-diagnosed-chronic-myeloid-leukemia-in-chronic-phase-long-term-follow-up-of-the-japanese-subgroup-of-the-randomized-enestnd-trial
#9
Hirohisa Nakamae, Tetsuya Fukuda, Chiaki Nakaseko, Yoshinobu Kanda, Ken Ohmine, Takaaki Ono, Itaru Matsumura, Akira Matsuda, Makoto Aoki, Kazuo Ito, Hirohiko Shibayama
In the ongoing, international, phase 3 study Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients (ENESTnd), nilotinib 300 and nilotinib 400 mg, both twice daily, are compared with imatinib 400 mg once daily for the treatment of newly diagnosed chronic myeloid leukemia in the chronic phase (CML-CP). Results for the overall population in ENESTnd (n = 846) showed that nilotinib resulted in higher response rates vs. imatinib and was well tolerated. Outcomes among Japanese patients in ENESTnd were specifically analyzed after 1 year of follow-up, and showed similar trends to the overall population; we present updated analysis of the Japanese subgroup based on 5 years of follow-up...
October 26, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29022901/bcr-abl1-induced-downregulation-of-wasp-in-chronic-myeloid-leukemia-involves-epigenetic-modification-and-contributes-to-malignancy
#10
Welbert O Pereira, Daniel D De Carvalho, Maria Emilia Zenteno, Beatriz F Ribeiro, Jacqueline F Jacysyn, Luiz R Sardinha, Maria A Zanichelli, Nelson Hamerschlak, Gareth E Jones, Katia B Pagnano, Fabiola A Castro, Yolanda Calle, Gustavo P Amarante-Mendes
Chronic myeloid leukemia (CML) is a myeloproliferative disease caused by the BCR-ABL1 tyrosine kinase (TK). The development of TK inhibitors (TKIs) revolutionized the treatment of CML patients. However, TKIs are not effective to those at advanced phases when amplified BCR-ABL1 levels and increased genomic instability lead to secondary oncogenic modifications. Wiskott-Aldrich syndrome protein (WASP) is an important regulator of signaling transduction in hematopoietic cells and was shown to be an endogenous inhibitor of the c-ABL TK...
October 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28939746/phase-iii-clinical-trial-rerise-study-results-of-efficacy-and-safety-of-radotinib-compared-with-imatinib-in-newly-diagnosed-chronic-phase-chronic-myeloid-leukemia
#11
Jae-Yong Kwak, Sung-Hyun Kim, Suk Joong Oh, Dae Young Zang, Hawk Kim, Jeong-A Kim, Young Rok Do, Hyeoung Joon Kim, Joon Seong Park, Chul Won Choi, Won Sik Lee, Yeung-Chul Mun, Jee Hyun Kong, Joo Seop Chung, Ho-Jin Shin, Dae-Young Kim, Jinny Park, Chul Won Jung, Udomsak Bunworasate, Narcisa Sonia Comia, Saengsuree Jootar, Arry Harryanto Reksodiputro, Priscilla B Caguioa, Sung-Eun Lee, Dong-Wook Kim
Purpose: Radotinib is a second-generation BCR-ABL1 tyrosine kinase inhibitor (TKI) approved in Korea for chronic phase chronic myeloid leukemia (CML-CP) in patients newly diagnosed or with insufficient response to other TKIs. This study was conducted to evaluate the efficacy and safety of radotinib as first-line therapy for CML-CP.Experimental Design: This multinational, open-label study assigned patients (1:1:1) to one of two twice-daily radotinib doses, or imatinib daily. The primary endpoint was major molecular response (MMR) by 12 months...
December 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28927784/safety-and-efficacy-of-blinatumomab-in-combination-with-a-tyrosine-kinase-inhibitor-for-the-treatment-of-relapsed-philadelphia-chromosome-positive-leukemia
#12
Rita Assi, Hagop Kantarjian, Nicholas J Short, Naval Daver, Koichi Takahashi, Guillermo Garcia-Manero, Courtney DiNardo, Jan Burger, Jorge Cortes, Nitin Jain, William Wierda, Salim Chamoun, Marina Konopleva, Elias Jabbour
OBJECTIVE: The treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia has been revolutionized with the introduction of tyrosine kinase inhibitors (TKIs) and the combination of these agents with chemotherapy. Blinatumomab is a bispecific anti-CD3/CD19 monoclonal antibody with clinical activity as single-agent in the relapsed setting and independent of BCR-ABL1 mutational status, including T315I. The combination of blinatumomab with a TKI may further improve outcomes for this high-risk population, including higher eradication of minimal residual disease and minimize the use of chemotherapy...
August 18, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28890835/ponatinib-as-a-valid-alternative-strategy-in-patients-with-blast-crisis-chronic-myeloid-leukemia-not-eligible-for-allogeneic-stem-cells-transplantation-and-or-conventional-chemotherapy-report-of-a-case
#13
Cristina Bucelli, Daniele Cattaneo, Valeria Ferla, Manuela Zappa, Caterina de Benedittis, Simona Soverini, Alessandra Iurlo
Currently, imatinib and dasatinib are the only tyrosine-kinase inhibitors approved in the US and Europe for the treatment of blast crisis of chronic myeloid leukemia (BC-CML) at diagnosis, while ponatinib is the only inhibitor used in patients bearing T315I mutation. Here we report the case of a 61-year-old man diagnosed with B-cell lymphoid BC-CML, initially treated with imatinib 800 mg day and then with dasatinib 140 mg day because of intolerance. A complete cytogenetic response (CCyR) was achieved at three months; however, three months later a relapse was observed, and the T315I mutation was detected...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28870619/a-causal-bayesian-network-model-of-disease-progression-mechanisms-in-chronic-myeloid-leukemia
#14
Daniel Koch, Robert S Eisinger, Alexander Gebharter
Chronic myeloid leukemia (CML) is a cancer of the hematopoietic system initiated by a single genetic mutation which results in the oncogenic fusion protein Bcr-Abl. Untreated, patients pass through different phases of the disease beginning with the rather asymptomatic chronic phase and ultimately culminating into blast crisis, an acute leukemia resembling phase with a very high mortality. Although many processes underlying the chronic phase are well understood, the exact mechanisms of disease progression to blast crisis are not yet revealed...
September 1, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28776669/hypomethylation-mediated-h19-overexpression-increases-the-risk-of-disease-evolution-through-the-association-with-bcr-abl-transcript-in-chronic-myeloid-leukemia
#15
Jing-Dong Zhou, Jiang Lin, Ting-Juan Zhang, Ji-Chun Ma, Xi-Xi Li, Xiang-Mei Wen, Hong Guo, Zi-Jun Xu, Zhao-Qun Deng, Wei Zhang, Jun Qian
Previous study has revealed that H19 expression is required for efficient tumor growth induced by BCR-ABL in chronic myeloid leukemia (CML). Herein, we further determined H19 expression and its clinical implication in patients with CML. H19 expression and methylation were detected by real-time quantitative PCR and real-time quantitative methylation-specific PCR, and then clinical implication of H19 expression was further analyzed. H19 expression was significantly up-regulated in CML patients (P < 0.001)...
August 4, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28762112/targeted-next-generation-sequencing-identifies-clinically-relevant-mutations-in-patients-with-chronic-neutrophilic-leukemia-at-diagnosis-and-blast-crisis
#16
S E Langabeer, K Haslam, J Kelly, J Quinn, R Morrell, E Conneally
PURPOSE: Chronic neutrophilic leukemia is a rare form of myeloproliferative neoplasm characterized by mature neutrophil hyperleukocytosis. The majority of patients harbor somatic mutations of CSF3R gene and are potentially amenable to targeted therapy with JAK inhibitors. The incidence and clinical significance of additional mutations requires clarification. MATERIALS AND METHODS: A next-generation sequencing approach for myeloid malignancy-associated mutations was applied to diagnostic and matched blast crisis samples from four chronic neutrophilic leukemia patients...
July 31, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28698852/acute-megakaryoblastic-blast-crisis-as-a-presentation-manifestation-of-chronic-myelogenous-leukemia
#17
Jenna B Bhattacharya, Richa Gupta, Amit Samadhiya
No abstract text is available yet for this article.
June 2017: Blood Research
https://www.readbyqxmd.com/read/28604385/differential-requirements-for-myeloid-leukemia-ifn-%C3%AE-conditioning-determine-graft-versus-leukemia-resistance-and-sensitivity
#18
Catherine Matte-Martone, Jinling Liu, Meng Zhou, Maria Chikina, Douglas R Green, John T Harty, Warren D Shlomchik
The graft-versus-leukemia (GVL) effect in allogeneic hematopoietic stem cell transplantation (alloSCT) is potent against chronic phase chronic myelogenous leukemia (CP-CML), but blast crisis CML (BC-CML) and acute myeloid leukemias (AML) are GVL resistant. To understand GVL resistance, we studied GVL against mouse models of CP-CML, BC-CML, and AML generated by the transduction of mouse BM with fusion cDNAs derived from human leukemias. Prior work has shown that CD4+ T cell-mediated GVL against CP-CML and BC-CML required intact leukemia MHCII; however, stem cells from both leukemias were MHCII negative...
June 30, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28588805/-chronic-myelogenous-leukemia-in-primary-blast-crisis-rather-than-de-novo-bcr-abl1-positive-acute-myeloid-leukemia
#19
Cedric Pastoret, Roch Houot
Differentiating chronic myelogenous leukemia in primary blast crisis (CML-BC) from de novo BCR-ABL1-positive acute myeloid leukemia (AML) is a diagnostic challenge with therapeutic consequences. In our case, a basophilia, the presence of the Philadelphia chromosome in all metaphases and the strict exclusion of molecular hallmarks of AML lead us to retain the diagnosis of CML-BC rather than BCR-ABL1+ AML.
June 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/28564659/life-threatening-intracerebral-hemorrhage-in-previously-undiagnosed-acute-t-cell-lymphoblastic-leukemia-with-blast-crisis-a-nightmare-in-neurosurgeon-s-life
#20
Abhay Singh, Rahul Gupta, Devender Chhonker, Gangesh Gunjan, Harjinder Singh Bhatoe
Spontaneous, nontraumatic intracerebral hemorrhage is a significant cause of morbidity and mortality throughout the world. Acute lymphoblastic leukemia is the most common cancer diagnosed in children. According to the literature, only 6 cases of acute lymphoblastic leukemia presenting as intracerebral hemorrhage have been reported. Five out of the 6 patients were managed conservatively; 3 out of these 6 patients survived with correction of coagulopathy. Surgical intervention was performed in only 1 of the previously reported cases in which the patient could not be salvaged...
2017: Pediatric Neurosurgery
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