Recent Progress in Chronic Neutrophilic Leukemia and Atypical Chronic Myeloid Leukemia

AbstractPurpose of ReviewWe reviewed recent diagnostic and therapeutic progress in chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML). We summarized recent genetic data that may guide future efforts towards implementing risk-adapted therapy based on mutational profile and improving disease control and survival of affected patients.Recent FindingsRecent genetic data in CNL and aCML prompted modifications to the World Health Organization (WHO) diagnostic criteria, which have improved our understanding of how CNL and aCML are different diseases despite sharing common findings of peripheral granulocytosis and marrow myeloid hyperplasia. The overlap of recurrently mutated genes between aCML and CMML support consideringCSF3R-T618I mutated cases as a distinct entity, either as CNL or CNL with dysplasia. Ongoing preclinical and clinical studies will help to further inform the therapeutic approach to these diseases.SummaryOur understanding of CNL and aCML has greatly advanced over the last few years. This will improve clarity for the diagnosis of these diseases, provide a strategy for risk stratification, and guide risk-adapted therapy.
Source: Current Hematologic Malignancy Reports - Category: Hematology Source Type: research

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Publication date: Available online 20 May 2019Source: Journal of Molecular Graphics and ModellingAuthor(s): Aramice Y.S. Malkhasian, Brendan J. HowlinAbstractMedicinal chemistry has in the past been dominated by learned insights from experienced organic chemists. However, with the advent of computer based methods, computer aided drug design has become prominent. We have compared here the ability of locally sourced expert medicinal chemists to purely automated methods and found that the automated method produces a better potential candidate drug than the expert input. The example chosen is based on inhibitors to Abl-kinase ...
Source: Journal of Molecular Graphics and Modelling - Category: Molecular Biology Source Type: research
Acta Haematol
Source: Acta Haematologica - Category: Hematology Source Type: research
Acta Haematol
Source: Acta Haematologica - Category: Hematology Source Type: research
GNF-2 is an allosteric inhibitor of Bcr-Abl. It was developed as a new class of anti-cancer drug to treat resistant chronic myelogenous leukemia. Recent studies suggest that c-Abl inhibition would provide a neuroprotective effect in animal models of Parkinson’s disease as well as in clinical trials. However, the role of c-Abl and effects of GNF-2 in glia-mediated neuroinflammation or pain hypersensitivity has not been investigated. Thus, in the present study, we tested the hypothesis that c-Abl inhibition by GNF-2 may attenuate the inflammatory activation of glia and the ensuing pain behaviors in animal models. Our r...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
ConclusionOur study suggests the influence of GSTM1 and GSTP1 polymorphisms on CML risk and treatment response. The interaction between GSTs polymorphisms and smoking plays a significant role on CML susceptibility.
Source: Molecular Genetics & Genomic Medicine - Category: Genetics & Stem Cells Authors: Tags: ORIGINAL ARTICLE Source Type: research
This report discusses the challenges associated with the management of newly diagnosed chronic phase CML in a patient with intolerance to multiple TKI therapies. PMID: 31091066 [PubMed]
Source: Journal of the National Comprehensive Cancer Network : JNCCN - Category: Cancer & Oncology Tags: J Natl Compr Canc Netw Source Type: research
We retrospectively evaluated the efficacy and safety of dasatinib among 48 Chinese patients with chronic phase chronic myeloid leukaemia. The proportions of patients achieving the optimal molecular responses at 3, 6, and 12  months, a major molecular response (MMR) rate and a complete cytogenetic response (CCyR) rate were 87.0, 87.0, 72.2, 45.8, and 72.7% for patients with dasatinib as second-line therapy, and 34.8, 34.8, 33.3, 20.8, and 46.2% as third-line therapy, respectively. A BCR-ABL1 transcript level on the Int ernational Scale (BCR-ABL1IS) of ≤10% at the initiation of ­dasatinib treatment was found to b...
Source: Acta Haematologica - Category: Hematology Source Type: research
Dasatinib (Bristol-Myers Squibb) is a short-acting inhibitor of multiple tyrosine kinases which is used orally in treatment of chronic myeloid leukemia, Philadelphia-chromosome positive acute Lymphoblastic leukemia (ALL), solid tumors and systemic mastocytosis [1]. Despite acceptable safety profile of dasatinib, cutaneous adverse reactions including xerosis, keratosis pilaris, pruritus, maculopapular/exfoliative rashes, edema, alopecia may limit its use in crucial conditions [2]. In case of drug-related cutaneous rashes, the primary approach is withdrawal of the culprit agent and introduction of supportive treatment.
Source: Annals of Allergy, Asthma and Immunology - Category: Allergy & Immunology Authors: Tags: Letters Source Type: research
In this study, we expressed human BCR-ABL1p210 and the resistant BCR-ABL1p210/T315I fusion oncogenes in Drosophila eyes. Expression of BCR-ABL1p210/T315I resulted in severe distortion of the ommatidial architecture of adult eyes and with more prominent rough eye phenotype compared to milder phenotypes in BCR-ABL1p210 reflecting a stronger oncogenic potential of the mutant. We then assessed the efficacy of the currently used tyrosine kinase inhibitors in BCR-ABL1p210 and BCR-ABL1p210/T315I expressing flies. Treatment of BCR-ABL1p210 expressing flies with potent kinase inhibitors (dasatinib and ponatinib) resulted in the res...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research
Strategies to stabilize remissions by specific elimination of residual acute myeloid leukemia (AML) blasts are needed. Leukemia-derived dendritic cell (DCleu/DC) generated from myeloid blasts improve antileukemic T-cell reactivity and install T-cell memory. Interferon (IFN)α-DC methods produce DCleu from chronic myeloid leukemia-patients (pts’) blood. Various INFα-containing versus other DC methods were studied to produce DCleu (evaluated by flowcytometry) from AML-pts’ blast-containing mononuclear (MNC) or whole blood (WB). After DCleu/DC stimulation in mixed lymphocyte cultures, T cells’ pot...
Source: Journal of Immunotherapy - Category: Allergy & Immunology Tags: Basic Studies Source Type: research
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