scholarly journals Deregulated hedgehog pathway signaling is inhibited by the smoothened antagonist LDE225 (Sonidegib) in chronic phase chronic myeloid leukaemia

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
David A. Irvine ◽  
Bin Zhang ◽  
Ross Kinstrie ◽  
Anuradha Tarafdar ◽  
Heather Morrison ◽  
...  
Keyword(s):  
Chronic Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Chronic Phase ◽  
Hedgehog Pathway

scholarly journals Clonal evolution and clinical implications of genetic abnormalities in blastic transformation of chronic myeloid leukaemia

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yotaro Ochi ◽  
Kenichi Yoshida ◽  
Ying-Jung Huang ◽  
Ming-Chung Kuo ◽  
Yasuhito Nannya ◽  
...  
Keyword(s):  
Chronic Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Kinase Inhibitors ◽  
Blast Crisis ◽  
Clonal Evolution ◽  
Chronic Phase ◽  
Genetic Alterations ◽  
Prognostic Impact ◽  
Genetic Abnormalities ◽  
Prior Use

AbstractBlast crisis (BC) predicts dismal outcomes in patients with chronic myeloid leukaemia (CML). Although additional genetic alterations play a central role in BC, the landscape and prognostic impact of these alterations remain elusive. Here, we comprehensively investigate genetic abnormalities in 136 BC and 148 chronic phase (CP) samples obtained from 216 CML patients using exome and targeted sequencing. One or more genetic abnormalities are found in 126 (92.6%) out of the 136 BC patients, including the RUNX1-ETS2 fusion and NBEAL2 mutations. The number of genetic alterations increase during the transition from CP to BC, which is markedly suppressed by tyrosine kinase inhibitors (TKIs). The lineage of the BC and prior use of TKIs correlate with distinct molecular profiles. Notably, genetic alterations, rather than clinical variables, contribute to a better prediction of BC prognosis. In conclusion, genetic abnormalities can help predict clinical outcomes and can guide clinical decisions in CML.

Low-dose dasatinib in older patients with chronic myeloid leukaemia in chronic phase (DAVLEC): a single-arm, multicentre, phase 2 trial

2021 ◽  
Vol 8 (12) ◽  
pp. e902-e911 ◽  
Author(s):  
Kazunori Murai ◽  
Hiroshi Ureshino ◽  
Takashi Kumagai ◽  
Hideo Tanaka ◽  
Kaichi Nishiwaki ◽  
...  
Keyword(s):  
Chronic Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Older Patients ◽  
Low Dose ◽  
Chronic Phase ◽  
Phase 2 ◽  
Multicentre Phase ◽  
Phase 2 Trial

scholarly journals Prognostic significance of cellular vascular endothelial growth factor (VEGF) expression in the course of chronic myeloid leukaemia

2009 ◽  
Vol 137 (7-8) ◽  
pp. 379-383 ◽  
Author(s):  
Ana Vidovic ◽  
Gradimir Jankovic ◽  
Dragica Tomin ◽  
Maja Perunicic-Jovanovic ◽  
Irena Djunic ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Chronic Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Prognostic Significance ◽  
Chronic Phase ◽  
Vascular Endothelial ◽  
Vegf Expression ◽  
Endothelial Growth Factor ◽  
The Impact

Introduction. Increased angiogenesis in bone marrow is one of the characteristics of chronic myeloid leukaemia (CML), a clonal myeloproliferative disorder that expresses a chimeric bcr/abl protein. Vascular endothelial growth factor (VEGF) is one of the most potent and a specific regulator of angiogenesis which principally targets endothelial cells and regulates several of their functions, including mitogenesis, permeability and migration. The impact of elevated VEGF expression on the course of chronic myeloid leukaemia is unknown. Objective. The aim of this study was the follow-up of VEGF expression during the course of CML. Methods. We studied VEGF expression of 85 CML patients (median age 50 years, range 16-75 years). At the commencement of the study, 29 patients were in chronic phase (CP), 25 in an accelerated phase (AP), and 31 in the blast crisis (BC). The temporal expression (percentage positivity per 1000 analysed cells) VEGF proteins over the course of CML were studied using the immunohistochemical technique utilizing relevant monoclonal antibodies. It was correlated with the laboratory (Hb, WBC and platelet counts, and the percentage of blasts) and clinical parameters (organomegaly, duration of CP, AP, and BC) of disease progression. Results. The expression of VEGF protein was most pronounced in AP (ANOVA, p=0.033). The level of VEGF expression correlated inversely with the degree of splenomegaly (Pearson, r=-0.400, p=0.011). High expression of VEGF correlated with a shorter overall survival (log rank, p=0.042). Conclusion. Immunohistochemically confirmed significance of the expression of VEGF in dependence of the CML stage could be of clinical importance in deciding on the timing therapy. These data suggest that VEGF plays a role in the biology of CML and that VEGF inhibitors should be investigated in CML.

scholarly journals Treatment-Free Remission in Chronic Myeloid Leukaemia: Can We Identify Prognostic Factors?

2021 ◽  
Author(s):  
Hilbeen Hisham Saifullah ◽  
Claire Marie Lucas
Keyword(s):  
Prognostic Factors ◽  
Chronic Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Kinase Inhibitors ◽  
Chronic Phase ◽  
Molecular Response ◽  
Predicting Success ◽  
Treatment Free Remission ◽  
Almost All ◽  
Tki Discontinuation

Following the development of tyrosine kinase inhibitors (TKI), the survival of patients with chronic myeloid leukaemia (CML) drastically improved. With the introduction of these agents, CML is now considered a chronic disease, for some patients. Taking into consideration the side effects, toxicity, and high cost, discontinuing TKIs became a goal for patients with chronic phase CML. Patients who achieved deep molecular response (DMR) and discontinued TKI, remained in treatment-free remission (TFR). Currently, the data from the published literature demonstrate that 40-60% of patients achieve TFR, with relapses occurring within the first six months. In addition, almost all patients who relapsed regained a molecular response upon re-treatment, indicating TKI discontinuation is safe. However, there is still a gap in the understanding the mechanisms behind TFR, and whether there are prognostic factors that can predict the best candidates who qualify for TKI discontinuation with a view to keeping them in TFR. Furthermore, the information about a second TFR attempt and the role of gradual de-escalation of TKI before complete cessation is limited. This review highlights the factors predicting success or failure of TFR. In addition, it ex-amines the feasibility of a second TFR attempt after the failure of the first one, and the current guidelines concerning TFR in clinical practice.

scholarly journals Rupture Spleen as Initial Presentation in A Patient of Chronic Myeloid Leukaemia: A Case Report

2016 ◽  
Vol 13 (2) ◽  
pp. 52-54
Author(s):  
Mohammad Ibrahim Khalil ◽  
Md. Nazmul Islam ◽  
Mafruha Akter ◽  
AZM Mostaque Hossain ◽  
Md. Amir Hossain
Keyword(s):  
Chronic Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Female Student ◽  
Care Center ◽  
Chronic Phase ◽  
Abdominal Distension ◽  
Emergency Laparotomy ◽  
Rare Presentation ◽  
Health Care Center ◽  
Common Presentation

A 22 years female student presented with sudden severe abdominal pain in left upper quadrant followed by abdominal distension. She attended in surgery unit of a tertiary health care center. On examination she was in shock and the abdomen was distended, tender. She was evaluated as  surgical acute abdomen and emergency laparotomy revealed rupture of spleen and splenectomy was done. Her CBC showed gross leucocytosis with predominance of neutrophils and significant number of myelocytes and the PBF showed the features of chronic phase of chronic myeloid leukaemia. BCR-ABL was positive from bone marrow that confirms the diagnosis. Splenomegaly is a common presentation of CML. However spontaneous rupture of spleen is a very rare presentation of CML. Journal of Science Foundation, 2015;13(2):52-54DOI: http://dx.doi.org/10.3329/jsf.v13i2.27935

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