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Chronic myeloid leukemia

Qie He, Junfeng Zhu, David Dingli, Jasmine Foo, Kevin Zox Leder
Over the past decade, several targeted therapies (e.g. imatinib, dasatinib, nilotinib) have been developed to treat Chronic Myeloid Leukemia (CML). Despite an initial response to therapy, drug resistance remains a problem for some CML patients. Recent studies have shown that resistance mutations that preexist treatment can be detected in a substantial number of patients, and that this may be associated with eventual treatment failure. One proposed method to extend treatment efficacy is to use a combination of multiple targeted therapies...
October 2016: PLoS Computational Biology
Paul B Koller, Hagop M Kantarjian, Graciela M Nogueras-Gonzalez, Elias Jabbour, Srdan Verstovsek, Gautam Borthakur, Zeev Estrov, William G Wierda, Guillermo Garcia-Manero, Alessandra Ferrajoli, Farhad Ravandi, Susan M O'Brien, Jorge E Cortes
BACKGROUND: Some patients with chronic myeloid leukemia (CML) have a history of previous malignancies. To the authors' knowledge, outcomes for CML diagnosed in these patients have not been well described. The current study was conducted to determine the outcome of patients with CML and a history of prior malignancies. METHODS: The current study included patients who were enrolled in clinical trials of tyrosine kinase inhibitors as initial therapy for CML in chronic phase from July 2000 to January 2014...
October 20, 2016: Cancer
Antonella Caivano, Francesco La Rocca, Vittorio Simeon, Marco Girasole, Simone Dinarelli, Ilaria Laurenzana, Angelo De Stradis, Luciana De Luca, Stefania Trino, Antonio Traficante, Giovanni D'Arena, Giovanna Mansueto, Oreste Villani, Giuseppe Pietrantuono, Luca Laurenti, Luigi Del Vecchio, Pellegrino Musto
PURPOSE: The use of extracellular vesicles (EVs) from body fluids as "liquid biopsies" is emerging as a promising approach for the diagnosis, prognosis and therapeutic monitoring of cancer patients. MicroRNA-155 (miR155), a non-coding transcript of the B-cell integration cluster (BIC) gene, has been reported to play a critical role in the pathogenesis of several types of hematologic malignancies (HMs) in which high miR155 levels have been found. At yet, however, the EV miR155 level and its putative clinical relevance in sera of HM patients have not been reported...
October 19, 2016: Cellular Oncology (Dordrecht)
Yoshitaka Sunami, Akihiko Gotoh, Naoki Watanabe, Yoko Edahiro, Yasuharu Hamano, Hironori Harada, Norio Komatsu
Pleural effusion may occur as a rare complication associated with myeloid hematological malignancies. However, it occasionally occurs in patients with myelodysplastic/myeloproliferative neoplasms(MDS/MPN), especially in chronic myelomonocytic leukemia(CMML)with marked leukocytosis. Pleural effusion can also develop in hematological disorders with bone marrow fibrosis. Here, we report a case of CMML with bone marrow fibrosis, in which massive pleural effusion developed rapidly during cytoreductive therapy with hydroxycarbamide(HU)...
October 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Annalisa Ruggeri, Yuqian Sun, Myriam Labopin, Andrea Bacigalupo, Francesca Lorentino, William Arcese, Stella Santarone, Zafar Gülbas, Didier Blaise, Giuseppe Messina, Ardeshi Ghavamzadeh, Florent Malard, Benedetto Bruno, Jose Luis Diez-Martin, Yener Koc, Fabio Ciceri, Mohamad Mohty, Arnon Nagler
Severe graft-versus-host-disease is a major barrier for non T-cell-depleted haploidentical stem cell transplantation and there is no consensus on the optimal GVHD prophylaxis. This study compared the two most commonly used graft-versus-host-disease prophylaxis regimens (post-transplant-cyclophosphamide-based (PTCY) versus the anti-thymocyte-globulin-based (ATG)) in adults with acute myeloid leukemia reported to the european society for blood and bone marrow transplantation. 308 patients were analyzed, 193 received PTCY and 115 ATG as anti- graft-versus-host-disease prophylaxis...
October 6, 2016: Haematologica
Surjit Singh, Pramod Kumar Sharma
Here, we present a case of chronic myeloid leukemia for which imatinib therapy was initated. Triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone was normal, and thyroid microsomal autoantibodies (TMA) were positive and patient was diagnosed as thyroiditis treated with corticosteroids for 1½ months which lead to resolution.
July 2016: Indian Journal of Pharmacology
Jing Huang, Leyan Wang, Chen Lu, Qun He, Yajing Xu, Fangping Chen, Xielan Zhao
OBJECTIVE: Previous studies compared the predictive ability of European Treatment Outcome Study (EUTOS), Sokal, and Hasford scoring systems and demonstrated inconsistent findings with unknown reason. This study is to determine a useful scoring system to predict the prognosis of patients with chronic myeloid leukemia (CML) and identify the probable factors that affect the scoring. MATERIALS AND METHODS: This is a retrospective cohort study. The predictive ability of EUTOS and the factors that affect scoring were analyzed in 234 Chinese CML-CP patients treated with front-line imatinib, including few patients temporarily administered hydroxyurea for cytoreduction before imatinib...
October 18, 2016: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
Ivana Milosevic
A 76-years old man presented with leucocytosis (86x109/l), fever, pneumonia and significant weight loss. He had a history of chronic lymphocytic leukemia diagnosed five years earlier and he responded with partial remission to the treatment with continuous low doses of chlorambucil. Analysis of blood smear, bone marrow aspiration and bone marrow biopsy revealed predomination of small lymphocytes, but 22% of cells were blasts negative to cytochemical stainings (Figure 1). Flow cytometric analysis showed two distinct populations: 65% of cells was small to moderate in size, CD19+, CD45+, CD5+, CD20+/-, but 30% of cells were large, CD34+, CD13+, HLA DR+, CD65+, CD45+, MPO weakly positive and CD33, CD14, CD15, CD16 negative...
October 18, 2016: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
Yali Chen, Qianxiang Zhou, Lei Zhang, Ran Wang, Meihua Jin, Yuling Qiu, Dexin Kong
Increasing resistance of imatinib, a BCR-ABL tyrosine kinase inhibitor, hinders its use in the therapy of chronic myeloid leukemia (CML). The PI3K pathway is known to be closely involved in BCR-ABL transformation and the tumorigenesis of CML, suggesting that PI3K may be a potential target for CML therapy. Idelalisib, a specific inhibitor of PI3K p110δ, has been approved for the treatment of chronic lymphocytic leukemia (CLL). However, the antileukemia effect of idelalisib on CML remains unknown. In the present study, the antileukemia activity of idelalisib alone or in combination with imatinib was investigated by use of K562 cells...
October 17, 2016: Oncology Reports
Govind Babu Kanakasetty, Lakshmaiah Kuntejowdahalli, Aditi Harsh Thanky, Lokanatha Dasappa, Linu Abraham Jacob, Suresh Babu Mallekavu, Prasanna Kumari
INTRODUCTION: Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by Philadelphia (Ph) chromosome with classical t(9;22)(q34;q11) seen in up to 90% of cases. However 5% to 10% of patients who present with variant Ph translocations (vPh) have been an area of research for their significance in predicting response to various therapies including tyrosine kinase inhibitors as well as prognosticating survival outcomes for many years involving varied patient populations, with conflicting results...
September 17, 2016: Clinical Lymphoma, Myeloma & Leukemia
Susannah O'Sullivan, Mei Lin Tay, Jian-Ming Lin, Usha Bava, Karen Callon, Jillian Cornish, Dorit Naot, Andrew Grey
Nilotinib and imatinib are tyrosine kinase inhibitors (TKIs) used in the treatment of chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GIST). In vitro, imatinib and nilotinib inhibit osteoclastogenesis, and in patients they reduce levels of bone resorption. One of the mechanisms that might underlie these effects is an increase in the production of osteoprotegerin (OPG). In the current work we report that platelet-derived growth factor receptor beta (PDGFRβ) signaling regulates OPG production in vitro...
2016: PloS One
Kazunori Nakase, Kenkichi Kita, Taiichi Kyo, Naoyuki Katayama
No abstract text is available yet for this article.
October 13, 2016: Leukemia & Lymphoma
Zofia Litwińska, Bogusław Machaliński
Chronic myeloid leukemia (CML) is a myeloproliferative disorder associated with clonal expansion of cancerous bone marrow stem cells. Tyrosine kinase inhibitors (TKIs) targeting Bcr-Abl oncoprotein are the first-line therapy for most CML patients, however, some are unresponsive to it or develop resistance. Recently, microRNAs (miRNAs) have been implicated in the progression of CML and the development of TKI resistance based on their important regulatory function in cell homeostasis. MicroRNAs are small noncoding RNAs that post-transcriptionally regulate gene expression...
October 13, 2016: Leukemia & Lymphoma
TaeHyung Kim, Marc S Tyndel, Hyeoung Joon Kim, Jae-Sook Ahn, Seung Hyun Choi, Hee Jeong Park, Yeo-Kyeoung Kim, Soo Young Kim, Jeffrey H Lipton, Zhaolei Zhang, Dennis Dong Hwan Kim
Somatic mutations commonly detected in a variety of myeloid neoplasms have not been systematically investigated in chronic myeloid leukemia (CML). We performed targeted deep sequencing on a total of 300 serial samples from 100 CML patients; thirty-seven patients carried mutations. Sixteen of these had evidence of mutations originating from preleukemic clones. Using unsupervised hierarchical clustering, we identified five distinct patterns of mutation dynamics arising following tyrosine kinase inhibitor (TKI) therapy...
October 12, 2016: Blood
Ya-Zhen Qin, Qian Jiang, Yue-Yun Lai, Hao Jiang, Hong-Xia Shi, Xiao-Su Zhao, Yan-Rong Liu, Xiao-Jun Huang
To investigate the impact of the combination of early molecular and cytogenetic responses on the achievement of MR4.5, 228 newly diagnosed chronic phase chronic myeloid leukemia patients treated with imatinib were categorized into 3-month and 6-month concordant optimal, discordant, concordant warning, and failure groups. Among them, 85.3% at 3 months and 78.1% at 6 months had concordant molecularly and cytogenetically defined responses. At both 3 and 6 months, patients with discordant, concordant warning and failure responses had similar 3-year MR4...
October 12, 2016: Leukemia & Lymphoma
Ayala Gover-Proaktor, Galit Granot, Saar Shapira, Oshrat Raz, Oren Pasvolsky, Arnon Nagler, Dorit L Lev, Aida Inbal, Ido Lubin, Pia Raanani, Avi Leader
Tyrosine kinase inhibitors (TKIs) have revolutionized the prognosis of chronic myeloid leukemia. With the advent of highly efficacious therapy, the focus has shifted toward managing TKI adverse effects, such as vascular adverse events (VAEs). We used an in vitro angiogenesis model to investigate the TKI-associated VAEs. Our data show that imatinib, nilotinib, and ponatinib reduce human umbilical vein endothelial cells (HUVECs) viability. Pharmacological concentrations of ponatinib induced apoptosis, reduced migration, inhibited tube formation of HUVECs, and had a negative effect on endothelial progenitor cell (EPC) function...
October 12, 2016: Leukemia & Lymphoma
Mrinal M Patnaik, Daniela Barraco, Terra L Lasho, Christy M Finke, Curtis A Hanson, Rhett P Ketterling, Naseema Gangat, Ayalew Tefferi
DNMT3A mutations are seen in ∼5% of patients with chronic myelomonocytic leukemia (CMML) and thus far, have had an indeterminate prognostic impact on survival. We carried out this study to assess the prognostic impact of DNMT3A mutations on a larger informative cohort of CMML patients (n=261). DNMT3A mutations were seen in 6% (n=16); 56% (n=9) male, with a median age of 64 years. Eighty-one % of DNMT3A mutations were missense, with the Arg882 mutational hot spot accounting for 63% of all changes. Five (31%) patients had an abnormal karyotype whereas concurrent gene mutations (SF3B1/SRSF2/U2AF1-56%, TET2-50%, and ASXL1-25%) were seen in all patients...
October 12, 2016: American Journal of Hematology
Shuai Dong, John C Byrd
The role of Lyn, both a positive and a negative regulator of B and myeloid cells, in chronic lymphocytic leukemia (CLL) has not been well characterized. In this issue of Cancer Cell, Nguyen et al. demonstrated that Lyn in macrophages rather than in CLL cells is critical for the malignancy.
October 10, 2016: Cancer Cell
Omkar Singh, Prabhat Agrawal, Ayush Agarwal, Sangeeta Yadav
No abstract text is available yet for this article.
January 2016: Journal of the Association of Physicians of India
Ghalaut Ps, Kumar S, Gaur N, Dahiya Hk, Chahal A
No abstract text is available yet for this article.
January 2016: Journal of the Association of Physicians of India
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