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https://www.readbyqxmd.com/read/27908728/activation-of-evi1-transcription-by-the-lef1-%C3%AE-catenin-complex-with-p53-alteration-in-myeloid-blast-crisis-of-chronic-myeloid-leukemia
#1
Nawin Manachai, Yusuke Saito, Shingo Nakahata, Avinash Govind Bahirvani, Tomomi Osato, Kazuhiro Morishita
The presence of a BCR-ABL1 fusion gene is necessary for the pathogenesis of chronic myeloid leukemia (CML) through t(9;22)(q34;q11) translocation. Imatinib, an ABL tyrosine kinase inhibitor, is dramatically effective in CML patients; however, 30% of CML patients will need further treatment due to progression of CML to blastic crisis (BC). Aberrant high expression of ecotropic viral integration site 1 (EVI1) is frequently observed in CML during myeloid-BC as a potent driver with a CML stem cell signature; however, the precise molecular mechanism of EVI1 transcriptional regulation during CML progression is poorly defined...
November 28, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27890073/switching-to-nilotinib-versus-imatinib-dose-escalation-in-patients-with-chronic-myeloid-leukaemia-in-chronic-phase-with-suboptimal-response-to-imatinib-lasor-a-randomised-open-label-trial
#2
Jorge E Cortes, Carmino Antonio De Souza, Manuel Ayala, Jose Luis Lopez, Eduardo Bullorsky, Sandip Shah, Xiaojun Huang, K Govind Babu, Kudrat Abdulkadyrov, José Salvador Rodrigues de Oliveira, Zhi-Xiang Shen, Tomasz Sacha, Israel Bendit, Zhizhou Liang, Tina Owugah, Tomasz Szczudlo, Sadhvi Khanna, Rafik Fellague-Chebra, Philipp D le Coutre
BACKGROUND: Optimal management of patients with chronic myeloid leukaemia in chronic phase with suboptimal cytogenetic response remains undetermined. This study aimed to investigate the safety and efficacy of switching to nilotinib vs imatinib dose escalation for patients with suboptimal cytogenetic response on imatinib. METHODS: We did a phase 3, open-label, randomised trial in patients with chronic myeloid leukaemia in chronic phase with suboptimal cytogenetic response to imatinib according to the 2009 European LeukemiaNet criteria, in Latin America, Europe, and Asia (59 hospitals and care centres in 12 countries)...
December 2016: Lancet Haematology
https://www.readbyqxmd.com/read/27784881/bilineal-extramedullary-blast-crisis-as-an-initial-presentation-of-chronic-myeloid-leukemia-a-case-report-and-literature-review
#3
Xiaoning Gao, Jie Li, Lili Wang, Ji Lin, Hongshi Jin, Yihan Xu, Nan Wang, Yu Zhao, Daihong Liu, Li Yu, Quanshun Wang
BACKGROUND Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder characterized by the Philadelphia chromosome generated by the reciprocal translocation t(9: 22)(q34;q11). CML is usually diagnosed in the chronic phase. Blast crisis represents an advanced phase of CML. Extramedullary blast crisis as the initial presentation of CML with bone marrow remaining in chronic phase is an unusual event. Further, extramedullary blast crisis with T lymphoid/myeloid bilineal phenotype as an initial presentation for CML is extremely unusual...
October 27, 2016: American Journal of Case Reports
https://www.readbyqxmd.com/read/27736287/high-expression-of-interleukin-2-receptor-%C3%AE-chain-cd25-in-myelodysplastic-syndrome-preceding-acute-myeloid-leukemia-and-chronic-myeloid-leukemia-in-myeloid-blast-crisis
#4
Kazunori Nakase, Kenkichi Kita, Taiichi Kyo, Naoyuki Katayama
No abstract text is available yet for this article.
October 13, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27721761/an-atypical-initial-presentation-of-chronic-myeloid-leukemia-with-central-nervous-system-and-lymph-node-blast-crises
#5
Khadega A Abuelgasim, Saeed Alshieban, Nada A Almubayi, Ayman Alhejazi, Abdulrahman R Jazieh
We describe the case of a young man with therapy-naive chronic myeloid leukemia who did not initially have any peripheral blood or bone marrow excess blasts but presented with extramedullary myeloid blast crises involving the central nervous system and multiple lymph nodes. Conventional cytogenetic tests were positive for t(9;22)(q34:q11) as well as for trisomy 8, 14 and 21 and del(16q). The patient's peripheral blood and bone marrow were positive for the BCR-ABL oncogene when analyzed by fluorescence in situ hybridization and polymerase chain reaction...
May 2016: Case Reports in Oncology
https://www.readbyqxmd.com/read/27628325/the-new-clinicopathologic-and-molecular-findings-in-myeloid-neoplasms-with-inv-3-q21q26-t-3-3-q21-q26-2
#6
Huan-You Wang, Hooman H Rashidi
CONTEXT: - Inv(3)(q21q26)/t(3;3)(q21;q26.2) is the most common form of genetic abnormality of the so-called 3q21q26 syndrome. Myeloid neoplasms with 3q21q26 aberrancies include acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and blast crisis of myeloproliferative neoplasms. Recent advances on myeloid neoplasms with inv(3)/t(3;3) with regard to clinicopathologic features and novel molecular or genomic findings warrant a comprehensive review on this topic. OBJECTIVE: - To review the clinicopathologic features and molecular as well as genomic alterations in myeloid neoplasms with inv(3)/t(3;3)...
December 2016: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/27605552/combined-targeting-of-bcl-2-and-bcr-abl-tyrosine-kinase-eradicates-chronic-myeloid-leukemia-stem-cells
#7
Bing Z Carter, Po Yee Mak, Hong Mu, Hongsheng Zhou, Duncan H Mak, Wendy Schober, Joel D Leverson, Bin Zhang, Ravi Bhatia, Xuelin Huang, Jorge Cortes, Hagop Kantarjian, Marina Konopleva, Michael Andreeff
BCR-ABL tyrosine kinase inhibitors (TKIs) are effective against chronic myeloid leukemia (CML), but they rarely eliminate CML stem cells. Disease relapse is common upon therapy cessation, even in patients with complete molecular responses. Furthermore, once CML progresses to blast crisis (BC), treatment outcomes are dismal. We hypothesized that concomitant targeting of BCL-2 and BCR-ABL tyrosine kinase could overcome these limitations. We demonstrate increased BCL-2 expression at the protein level in bone marrow cells, particularly in Lin(-)Sca-1(+)cKit(+) cells of inducible CML in mice, as determined by CyTOF mass cytometry...
September 7, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27584557/cml-in-chronic-phase-with-novel-secondary-cytogenetic-abnormalities-a-case-report
#8
Hiral S Patel, Manisha M Brahmbhatt, Pina J Trivedi, Dharmesh M Patel, Ankita A Sugandhi, Binita V Patel, Prabhudas S Patel
The clonal evolution in t(9;22)-positive Chronic Myelocytic Leukemia (CML) patients is well established. Four major changes occur in more than 70% of patients: +8, i(17q), +19, and an extra Philadelphia chromosome. Here, we present a case with CML-Chronic phase (CML-CP) and novel t(9;13)(q34;q12~13) in addition to t(9;22)(q34;q11.2). Fluorescence in situ hybridization (FISH) using dual color dual fusion probe analysis on interphase and metaphase cells confirmed the t(9;13)(q34;q12~13) as clonal evolution and secondary event to Philadelphia chromosome...
2016: Journal of the Association of Genetic Technologists
https://www.readbyqxmd.com/read/27581149/new-mouse-models-to-investigate-the-efficacy-of-drug-combinations-in-human-chronic-myeloid-leukemia
#9
Hanyang Lin, Adrian Woolfson, Xiaoyan Jiang
Chronic myeloid leukemia (CML) comprises a simple and effective paradigm for generating new insights into the cellular origin, pathogenesis, and treatment of many types of human cancer. In particular, mouse models of CML have greatly facilitated the understanding of the underlying molecular mechanisms and pathogenesis of this disease and have led to the identification of new drug targets that in some cases offer the possibility of functional cure. There are currently three established CML mouse models: the BCR-ABL transgenic model, the BCR-ABL retroviral transduction/transplantation model, and the xenotransplant immunodeficient model...
2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27581146/a-convenient-cell-culture-model-for-cml-acquired-resistance-through-bcr-abl-mutations
#10
Zhiqiang Wang, WenYong Chen
Tyrosine kinase inhibitors (TKIs) are the effective treatments for chronic myeloid leukemia (CML). However, clinical resistance to TKIs that leads to patient relapse remains a challenge. Acquisition of BCR-ABL mutations is crucial in the resistance but the underlying molecular mechanisms are poorly understood. Here we describe a cell culture model for CML acquired resistance in which blast crisis CML cells undergo initial apoptosis upon treatment with therapeutically effective doses of TKIs, but the cells regrow quickly with development of resistance through BCR-ABL mutations...
2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27564459/extramedullary-sudden-blast-crisis-in-chronic-phase-chronic-myeloid-leukemia-during-first-line-treatment-with-nilotinib
#11
M K Angelopoulou, J V Asimakopoulos, Z Galani, G Levidou, M Roumelioti, T P Vassilakopoulos, P Korkolopoulou, P Panayiotidis
No abstract text is available yet for this article.
2016: Blood Cancer Journal
https://www.readbyqxmd.com/read/27538509/is-going-for-cure-in-cml-targeting-aberrant-glycogen-synthase-kinase-3%C3%AE
#12
Concetta Saponaro, Michele Maffia, Nicola Di Renzo, Addolorata Maria Luce Coluccia
Chronic Myelogenous Leukemia (CML)-initiating cells (CICs) express the hybrid oncoprotein BCR-ABL at the highest levels compared to their differentiated progeny but fail to expand at the same rate as downstream leukemic myeloid cells. Moreover, the primitive stem cell clone that originates the indolent CML chronic phase (CP) remains almost invariant as the disease evolves to a fatal blast crisis (BC). Compared to their healthy counterpart, the most dormant BCR-ABL+ CICs show the tendency to remain in a somewhat unusual 'proliferative quiescence', i...
August 17, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/27537935/philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-is-separated-into-two-subgroups-associated-with-survival-by-bcr-abl-fluorescence-in-situ-hybridization-of-segmented-cell-nuclei-report-from-a-single-institution
#13
Yoshimasa Kamoda, Kiyotaka Izumi, Futoshi Iioka, Takashi Akasaka, Fumihiko Nakamura, Chiyuki Kishimori, Katsuyo Tsuda, Katsuhiro Fukutsuka, Atsuko Okumura, Masahiko Hayashida, Hitoshi Ohno
Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) may include the lymphoid blast crisis of chronic myeloid leukemia (CML-BC). We applied fluorescence in situ hybridization (FISH) of the BCR-ABL fusion gene to peripheral blood and/or bone marrow smears to determine whether the fusion was restricted to mononuclear cell nuclei or if segmented cell nuclei representing mature neutrophils also carried the fusion (Seg-FISH). Among 20 patients with Ph+ ALL without a prior diagnosis of CML, 9 were Seg-FISH+ and 11 were Seg-FISH-...
2016: Acta Haematologica
https://www.readbyqxmd.com/read/27531771/-comparative-analysis-of-efficacy-and-drug-resistance-of-imatinib-in-patients-with-chronic-myeloid-leukemia-at-chronic-and-advanced-phases
#14
Wei Wang, Hai-Bo Liu, Mei Zhang
OBJECTIVE: To compare the efficacy and drug resistance of imatinib in patients with chronic myeloid leukemia (CML) at chronic phase (CP) and advanced phase (accelerated phase and blast crisis (AP+BC). METHODS: Forty-two patients with CML were treated with imatinib of different doses(CP 400 mg/d, AP+BC 600 mg/d), and the efficacy and drug resistance of the 2 groups were compared. The median follow-up time was 24 months (3-42 months). RESULTS: The complete hematological remission rate (CHR), the major cytogenetic remission rate (MCyR) and complete molecular remission rate (CMoR) in the CP group were 100%, 89...
August 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/27519941/high-abundance-of-circulating-megakaryocytic-cells-in-chronic-myeloid-leukemia-in-indian-patients-revisiting-george-minot-to-re-interpret-megakaryocytic-maturation
#15
Mona Anand, Biswadip Hazarika, Lalit Kumar, Rajive Kumar, Anita Chopra
Circulating megakaryocytic cells abound in chronic myeloid leukemia (CML) seen in India and uniquely provide a setting for observing megakaryocytic maturation in the peripheral blood, a milieu not native to megakaryocytes. Peripheral blood megakaryocytic cells were studied in 324 cases of CML (235 chronic, 65 accelerated and 24 blastic phases). Two maturation themes were evident. Megakaryocytic blasts, especially in some cases of blast crisis, precociously make a foray into platelet formation and end up producing huge agranular or poorly granular cytoplasmic lobulated masses, that break off and come to lie in the circulation...
September 2016: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/27511749/case-of-cml-lymphoid-blast-crisis-presenting-as-bilateral-breast-masses
#16
Aneesha Hossain, Kanika Gupta, Andrew Mener, Imad Tabbara
A woman aged 42 years with a 1-month history of rapidly expanding bilateral breast masses presented with severe leucocytosis, anaemia, blurry vision, headaches and shortness of breath. Evaluation revealed chronic myeloid leukaemia in lymphoid blast crisis with extramedullary leukaemia involving her breasts.
2016: BMJ Case Reports
https://www.readbyqxmd.com/read/27501474/outcomes-with-frontline-nilotinib-treatment-in-turkish-patients-with-newly-diagnosed-philadelphia-chromosome-positive-chronic-myeloid-leukemia-in-chronic-phase
#17
Guray Saydam, Ibrahim Celalettin Haznedaroglu, Leylagul Kaynar, Akif S Yavuz, Ridvan Ali, Birol Guvenc, Olga M Akay, Zafer Baslar, Ugur Ozbek, Mehmet Sonmez, Demet Aydin, Mustafa Pehlivan, Bulent Undar, Simten Dagdas, Orhan Ayyildiz, Diyar Z Akkaynak, Ilkiz M Dag, Osman Ilhan
OBJECTIVE: Nilotinib is a BCR-ABL1 tyrosine kinase inhibitor approved for the treatment of patients with chronic myeloid leukemia in chronic phase (CML-CP). This study was the first prospective evaluation of the efficacy and safety of nilotinib in Turkish patients with newly diagnosed CML-CP. The primary endpoint of the study was the rate of major molecular response (MMR; BCR-ABL1 ≤ 0.1% on the International Scale [BCR-ABL1(IS)]) by 12 months. METHODS: Patients with newly diagnosed CML-CP were treated with nilotinib 300 mg twice daily...
October 2016: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/27434016/very-long-survival-in-complete-cytogenetic-remission-in-an-adolescent-with-lymphoid-blast-crisis-of-chronic-myeloid-leukemia-after-treatment-with-intensive-all-directed-chemotherapy-combined-with-continuous-imatinib
#18
Alexey Maschan, Galina Novichkova, Natalia Miakova, Marina Persiantseva
An 11-year-old male was diagnosed with chronic-phase chronic myeloid leukemia (CML) in 1998 and received therapy with interferon-α2b and low-dose cytarabine. In 6 years, he progressed to lymphoid blast crisis and received induction chemotherapy with prednisolone, vincristine, daunorubicin, and l-asparaginase concomitantly with imatinib 400 mg/day, and continuation with vincristine + prednisolone, cytarabine + etoposide, vincristine + l-asparaginase, cyclophosphamide + etoposide, and 6-mercaptopurine + methotrexate...
July 19, 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27428357/advanced-phase-chronic-myeloid-leukaemia-cml-in-the-tyrosine-kinase-inhibitor-era-a-report-from-the-swedish-cml-register
#19
Stina Söderlund, Torsten Dahlén, Fredrik Sandin, Ulla Olsson-Strömberg, Maria Creignou, Arta Dreimane, Anna Lübking, Berit Markevärn, Anders Själander, Hans Wadenvik, Leif Stenke, Johan Richter, Martin Höglund
OBJECTIVES: The primary goal in management of chronic phase (CP) chronic myeloid leukaemia (CML) is to prevent disease progression to accelerated phase (AP) or blast crisis (BC). We have evaluated progression rates in a decentralised healthcare setting and characterised patients progressing to AP/BC on TKI treatment. METHODS: Using data from the Swedish CML register, we identified CP-CML patients diagnosed 2007-2011 who progressed to AP/BC within 2 yrs from diagnosis (n = 18) as well as patients diagnosed in advanced phase during 2007-2012 (n = 36) from a total of 544 newly diagnosed CML cases...
July 18, 2016: European Journal of Haematology
https://www.readbyqxmd.com/read/27416909/the-clinical-significance-of-abcb1-overexpression-in-predicting-outcome-of-cml-patients-undergoing-first-line-imatinib-treatment
#20
L N Eadie, P Dang, V A Saunders, D T Yeung, M P Osborn, A P Grigg, T P Hughes, D L White
Tyrosine kinase inhibitor (TKI) therapy results in excellent responses in the majority of patients with chronic myeloid leukaemia. First-line imatinib treatment, with selective switching to nilotinib when patients fail to meet specific molecular targets or for imatinib intolerance, results in excellent overall molecular responses and survival. However, this strategy is less effective in cases of primary imatinib resistance; moreover, 25% of patients develop secondary resistance such that 20-35% of patients initially treated with imatinib will eventually experience treatment failure...
July 15, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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