The complex karyotype in hematological malignancies: a comprehensive overview by the Francophone Group of Hematological Cytogenetics (GFCH).

Karyotype complexity has major prognostic value in many malignancies. There is no consensus on the definition of a complex karyotype, and the prognostic impact of karyotype complexity differs from one disease to another. Due to the importance of the complex karyotype in the prognosis and treatment of several hematological diseases, the Francophone Group of Hematological Cytogenetics (Groupe Francophone de Cytogénétique Hématologique, GFCH) has developed an up-to-date, practical document for helping cytogeneticists to assess complex karyotypes in these hematological disorders.

RBM22, a Key Player of Pre-mRNA Splicing and Gene Expression Regulation, Is Altered in Cancer.

RNA-Binding Proteins (RBP) are very diverse and cover a large number of functions in the cells. This review focuses on RBM22, a gene encoding an RBP and belonging to the RNA-Binding Motif (RBM) family of genes. RBM22 presents a Zinc Finger like and a Zinc Finger domain, an RNA-Recognition Motif (RRM), and a Proline-Rich domain with a general structure suggesting a fusion of two yeast genes during evolution: and .

TP53 in Myelodysplastic Syndromes.

Myelodysplastic syndromes (MDSs) are heterogeneous for their morphology, clinical characteristics, survival of patients, and evolution to acute myeloid leukemia. Different prognostic scoring systems including the International Prognostic Scoring System (IPSS), the Revised IPSS, the WHO Typed Prognostic Scoring System, and the Lower-Risk Prognostic Scoring System have been introduced for categorizing the highly variable clinical outcomes. However, not considered by current MDS prognosis classification systems, gene variants have been identified for their contribution to the clinical heterogeneity of the disease and their impact on the prognosis.

ETV6-RUNX1 and RUNX1 directly regulate RAG1 expression: one more step in the understanding of childhood B-cell acute lymphoblastic leukemia leukemogenesis.

ETV6-RUNX1 and RUNX1 directly promote expression. ETV6-RUNX1 and RUNX1 preferentially bind to the −1200 bp enhancer of and the −80 bp promoter of gene respectively, and compete for these bindings. ETV6-RUNX1 and RUNX1 induce an excessive RAG recombinase activity.

Fluorescent In Situ Hybridization Must be Preferred to pan-TRK Immunohistochemistry to Diagnose NTRK3-rearranged Gastrointestinal Stromal Tumors (GIST).

Tyrosine kinase inhibitors have revolutionized the treatment of patients with gastrointestinal stromal tumors (GISTs). Nevertheless, some GISTs do not contain any targetable KIT or PDGFRA mutations classically encountered in this field. Novel approved therapies targeting TRK chimeric proteins products of NTRK genes fusions consist in a promising approach to treat some patients with GISTs lacking any identified driver oncogenic mutation in KIT, PDGFRA or BRAF genes.

Decrease of spermatozoa with an unbalanced chromosome content after cell sorting in men carrying a structural chromosomal abnormality.

Background: We showed that in men with a constitutional chromosomal abnormality, DNA fragmentation was significantly higher in chromosomally unbalanced spermatozoa than in spermatozoa with a normal or balanced chromosomal content. These results could be explained by a phenomenon already described in infertile men: abortive apoptosis.

Objectives: To determine whether magnetic-activated cell separation could select spermatozoa with lower levels of DNA fragmentation and unbalanced chromosome content in men carrying a structural chromosomal abnormality.

17p deletion strongly influences rituximab elimination in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia and the anti-CD20 monoclonal antibody, rituximab, represents the therapeutic gold standard for more than 2 decades in this pathology, when used in combination with chemotherapy. However, some patients experience treatment resistance or rapid relapses, and in particular, those harboring a 17p/TP53 deletion (del(17p)). This resistance could be explained by a chemo-resistance, but it could also result from the direct impact of del(17p) on the pharmacokinetics of rituximab, which represents the aim of the present study.

Combining cytogenetic and epigenetic approaches in chronic lymphocytic leukemia improves prognosis prediction for patients with isolated 13q deletion.

Background: Both defective DNA methylation and active DNA demethylation processes are emerging as important risk factors in chronic lymphocytic leukemia (CLL). However, associations between 5-cytosine epigenetic markers and the most frequent chromosomal abnormalities detected in CLL remain to be established.

Methods: CLL patients were retrospectively classified into a cytogenetic low-risk group (isolated 13q deletion), an intermediate-risk group (normal karyotype or trisomy 12), and a high-risk group (11q deletion, 17p deletion, or complex karyotype [≥ 3 breakpoints]).

Alterations in DNA methylation/demethylation intermediates predict clinical outcome in chronic lymphocytic leukemia.

Cytosine derivative dysregulations represent important epigenetic modifications whose impact on the clinical outcome in chronic lymphocytic leukemia (CLL) is incompletely understood. Hence, global levels of 5-methylcytosine (5-mCyt), 5-hydroxymethylcytosine (5-hmCyt), 5-carboxylcytosine (5-CaCyt) and 5-hydroxymethyluracil were tested in purified B cells from CLL patients ( = 55) and controls ( = 17). The DNA methylation 'writers' (DNA methyltransferases []), 'readers' (methyl-CpG-binding domain []), 'editors' (ten-eleven translocation []) and 'modulators' () were also evaluated.

Prognostic impact of p15 gene aberrations in acute leukemia.

The p15 gene (also known as CDKN2B, INK4B, p15), located in band 9p21, encodes a protein that induces a G1-phase cell cycle arrest through inhibition of CDK4/6 (cyclin-dependent kinase 4/6). It also plays an important role in the regulation of cellular commitment of hematopoietic progenitor cells and myeloid cell differentiation. p15 can be silenced by several mechanisms, including deletion and hypermethylation of its promoter.

Geographic/ethnic variability of chromosomal and molecular abnormalities in leukemia.

In 1963, Jean Bernard, a French hematologist, opened a new chapter in hematology called geographic hematology ('Hématologie Géographique'). He distinguished two research avenues. One dealt with the differences between the various populations (ethnic hematology), the other with various environmental factors (environmental hematology).