1,721,044 research outputs found
The JAK2 GGCC (46/1) haplotype in myeloproliferative neoplasms: Causal or random?
Full text linkThe germline JAK2 haplotype known as “GGCC or 46/1 haplotype” (haplotypeGGCC_46/1) consists of a combination of single nucleotide polymorphisms (SNPs) mapping in a region of about 250 kb, extending from the JAK2 intron 10 to the Insulin-like 4 (INLS4) gene. Four main SNPs (rs3780367, rs10974944, rs12343867, and rs1159782) generating a “GGCC” combination are more frequently indicated to represent the JAK2 haplotype. These SNPs are inherited together and are frequently associated with the onset of myeloproliferative neoplasms (MPN) positive for both JAK2 V617 and exon 12 mutations. The association between the JAK2 haplotypeGGCC_46/1and mutations in other genes, such as thrombopoietin receptor (MPL) and calreticulin (CALR), or the association with triple negative MPN, is still controversial. This review provides an overview of the frequency and the role of the JAK2 haplotypeGGCC_46/1in the pathogenesis of different myeloid neoplasms and describes the hypothetical mechanisms at the basis of the association with JAK2 gene mutations. Moreover, possible clinical implications are discussed, as different papers reported contrasting data about the correlation between the JAK2 haplotypeGGCC_46/1and blood cell count, survival, or disease progression
CPX-351 in acute myeloid leukemia: can a new formulation maximize the efficacy of old compounds?
No full textIntroduction: The management of Acute Myeloid Leukemia (AML) (with the exception of acute promyelocytic leukemia) has remained largely unchanged over the past 40Â years. In particular, patients defined as high-risk, according to the 2017 European Leukemia Net recommendations, represent a subgroup with poor response to current therapies that are frequently associated with high-grade toxicity and potentially fatal complications. Areas covered: Preliminary results from an ongoing phase III clinical trial suggest that CPX-351 could represent an interesting treatment option in both induction and âbridge-to-transplantâ settings. In particular, 60- to 75-year-old patients with secondary AML, when treated with CPX-351, exhibit superior overall survival (HRÂ =Â 0.69; PÂ =Â 0.005; median OS 9.56 vs. 5.95Â months), event free survival (HRÂ =Â 0.74; PÂ =Â 0.021), and composite response rate (47.7% vs. 33.3%; PÂ =Â 0.016) as compared to standard â7Â +Â 3â therapy. Herein, we detail the main pharmacological features of CPX-351 and review updated results of clinical trials investigating its employment in AML. Expert commentary: Novel liposome-based drugs display a high therapeutic index and represent a promising alternative to unencapsulated drugs, especially when high-risk features complicate the use of standard treatments. Further efforts in both understanding AML biology and improving nanodrug design are needed
Monosomal karyotype in myeloid neoplasias: a literature review
Full text linkIn 2008, the concept of the monosomal karyotype (MK) in adult acute myeloid leukemia (AML) patients was introduced, defined by the presence of a chromosomal aberration pattern characterized by the presence of at least two autosomal monosomies or of one monosomy plus one or more structural aberrations (not including loss of a chromosome). We present a systematic review of the literature about the influence of the MK on the outcome of patients affected by myeloid malignancies (AML, myelodysplastic syndromes, and primary myelofibrosis). For this review, a comprehensive literature search using the term "monosomal karyotype" was performed, considering articles listed in MEDLINE. This analysis of the literature confirms the negative prognostic impact on survival of the MK in myeloid neoplasias. The detrimental effect of MK on AML patients' outcome is independent of other variables, including adverse cytogenetic features, supporting the identification of this entity as a challenging subgroup of patients with distinct biologic and clinical features
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Molecular cytogenetic findings supporting the evidence of a biclonal origin in acute myeloid leukemia
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"Home-brew" FISH assay shows higher efficiency than BCR-ABL dual color, dual fusion probe in detecting microdeletions and complex rearrangements associated with t(9;22) in chronic myeloid leukemia
No full textWe carried out fluorescence in situ hybridization (FISH) studies on 18 Ph+ chronic myeloid leukemia (CML) cases with chromosome 22 genomic deletions with the Vysis BCR-ABL dual-color/dual-fusion probe (BCR-ABL DC/DF) to compare the hybridization patterns obtained with this approach to those obtained with the "home brew" BAC/PAC system. Our results are the following: chromosome 22 microdeletions less than 400 kilobases (Kb) were not detected by the BCR DC/DF probe; FISH analysis with the BCR DC/DF probe in cases bearing chromosome 22 microdeletions ranging from 400 to 700 Kb produced a faint signal on the der(9); and the BCR-ABL DC/DF FISH pattern was comparable to the one obtained by the home brew probe in the presence of a 900-Kb chromosome 22 microdeletion. Our home-brew FISH system represents an accurate method for revealing a subset of CML patients with der(9) microdeletions. © 2007 Elsevier Inc. All rights reserved
Characterization of der(9) deletions in CML patients
No full textDeletionsadjacenttothe9/22translocationbreakpointonthederivativechromosome9haverecentlybeendescribedina substantialnumberofchronicmyeloidleukemia(CML)cases,buttheirextensionhasnotbeencharacterizedindetail.Using FISHwithanappropriatesetofBAC/PACprobes,wehavecharacterizedthedeletionin10CMLcases, identifiedbyscreening 71patientsatdiagnosis.Fivepatientsshowedacomplexchromosomerearrangementand3ofthemweredeleted.Thesizeofthe deletionwasvariable, rangingfromfewhundredskbto8Mb.Aminimallydeletedregiononbothchromosomes9and22was identifiedandwasfoundtocontaintheASSgeneonchromosome9andIGLL1onchromosome2
A chronic myelocytic leukemia case bearing deletions on the three chromosomes involved in a variant t(9;22;11)
No full textGenomic deletions on the derivative chromosomes bearing the reciprocal fusion gene have recently been reported in chronic myelocytic leukemia (CML). We here describe a CML case with a variant rearrangement t(9;22;11)(q34;q11;q13) showing the loss of chromosome 11 sequences in addition to der(9) deletions. Known tumor suppressor genes involved in apoptosis and in the control of cell proliferation were found to be mapped to the lost sequences. Our findings indicate that genomic deletions may occur also on the third derivative chromosome in variant t(9;22)
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