In chronic lymphocytic leukaemia, SLAMF1 deregulation is associated with genomic complexity and independently predicts a worse outcome.

In a series of 349 patients with chronic lymphocytic leukaemia (CLL), we found lower levels of signalling lymphocytic activation molecule family member 1 (SLAMF1) expression in cases with highly complex karyotypes, as defined by the presence of five or more chromosomal abnormalities (CK5; P < 0·001) and with major chromosomal structural abnormalities (P < 0·001). SLAMF1 downregulation was significantly associated with advanced Binet Stage (P = 0·001), CD38 positivity (P < 0·001), high β -microglobulin levels (P < 0·001), immunoglobulin heavy chain variable region gene (IGHV) unmutated status (P < 0·001), 11q deletion (P < 0·001), tumour protein p53 (TP53) disruption (P = 0·011) and higher risk CLL International Prognostic Index categories (P < 0·001). Multivariate analysis showed that downregulated SLAMF1 levels had independent negative prognostic impact on time-to-first treatment (P < 0·001) and overall survival (P < 0·001).

Biological significance and prognostic/predictive impact of complex karyotype in chronic lymphocytic leukemia.

The complex karyotype (CK) is an established negative prognostic marker in a number of haematological malignancies. After the introduction of effective mitogens, a growing body of evidence has suggested that the presence of 3 or more aberrations by conventional banding analysis (CBA) is associated with an unfavorable outcome in chronic lymphocytic leukemia (CLL). Thus, the importance of CBA was recognized by the 2018 guidelines of the International Workshop on CLL, which proposed the introduction of CBA in clinical trials to validate the value of karyotype aberrations.

In chronic lymphocytic leukaemia with complex karyotype, major structural abnormalities identify a subset of patients with inferior outcome and distinct biological characteristics.

Complex karyotype (CK) is a negative prognostic factor in chronic lymphocytic leukaemia (CLL). However, CK is a heterogeneous cytogenetic category. Unbalanced rearrangements were present in 73·3% of 90 CLL patients with CK (i.

An extensive molecular cytogenetic characterization in high-risk chronic lymphocytic leukemia identifies karyotype aberrations and TP53 disruption as predictors of outcome and chemorefractoriness.

We investigated whether karyotype analysis and mutational screening by next generation sequencing could predict outcome in 101 newly diagnosed chronic lymphocytic leukemia patients with high-risk features, as defined by the presence of unmutated IGHV gene and/or 11q22/17p13 deletion by FISH and/or TP53 mutations. Cytogenetic analysis showed favorable findings (normal karyotype and isolated 13q14 deletion) in 30 patients, unfavorable (complex karyotype and/or 17p13/11q22 deletion) in 34 cases and intermediate (all other abnormalities) in 36 cases. A complex karyotype was present in 21 patients.

Identifying High-Risk Chronic Lymphocytic Leukemia: A Pathogenesis-Oriented Appraisal of Prognostic and Predictive Factors in Patients Treated with Chemotherapy with or without Immunotherapy.

Chronic lymphocytic leukemia (CLL) displays an extremely variable clinical behaviour. Accurate prognostication and prediction of response to treatment are important in an era of effective first-line regimens and novel molecules for high risk patients. Because a plethora of prognostic biomarkers were identified, but few of them were validated by multivariable analysis in comprehensive prospective studies, we applied in this survey stringent criteria to select papers from the literature in order to identify the most reproducible prognostic/predictive markers.

Extensive next-generation sequencing analysis in chronic lymphocytic leukemia at diagnosis: clinical and biological correlations.

Background: In chronic lymphocytic leukemia (CLL), next-generation sequencing (NGS) analysis represents a sensitive, reproducible, and resource-efficient technique for routine screening of gene mutations.

Methods: We performed an extensive biologic characterization of newly diagnosed CLL, including NGS analysis of 20 genes frequently mutated in CLL and karyotype analysis to assess whether NGS and karyotype results could be of clinical relevance in the refinement of prognosis and assessment of risk of progression. The genomic DNA from peripheral blood samples of 200 consecutive CLL patients was analyzed using Ion Torrent Personal Genome Machine, a NGS platform that uses semiconductor sequencing technology.

Cytogenetic and molecular cytogenetic profile of bone marrow-derived mesenchymal stromal cells in chronic and acute lymphoproliferative disorders.

The possibility that human mesenchymal stromal cells (hMSC) may derive from the malignant clone in hematological malignancies (HM) is a controversial issue. In order to clarify hMSC origin and disclose possible cytogenetic heterogeneity in hMSC belonging to different patients, bone marrow (BM)-derived hMSC samples from chronic lymphocytic leukemia (CLL) and acute lymphoblastic leukemia (ALL) were expanded in culture, characterized by flow cytometry, and screened by conventional cytogenetic analysis and fluorescent in situ hybridization for the presence of possible cytogenetic aberrations, related or not to the hematopoietic neoplastic clone. Our data showed that the presence of cytogenetic aberrations in successfully expanded HM-MSC stromal layers derives from the persistence of contaminating hemopoietic cells (HC), which is greatly supported by in vitro culture conditions that could mimic in vivo microenvironmental niche.

Chromosome aberrations detected by conventional karyotyping using novel mitogens in chronic lymphocytic leukemia with "normal" FISH: correlations with clinicobiologic parameters.

It is unclear whether karyotype aberrations that occur in regions uncovered by the standard fluorescence in situ hybridization (FISH) panel have prognostic relevance in chronic lymphocytic leukemia (CLL). We evaluated the significance of karyotypic aberrations in a learning cohort (LC; n = 64) and a validation cohort (VC; n = 84) of patients with chronic lymphocytic leukemia with "normal" FISH. An abnormal karyotype was found in 21.

Clonal evolution including 14q32/IGH translocations in chronic lymphocytic leukemia: analysis of clinicobiologic correlations in 105 patients.

To better define the significance of clonal evolution (CE) including 14q32 translocations involving the immunoglobulin heavy chain gene (IGH) in chronic lymphocytic leukemia (CLL), 105 patients were analyzed sequentially by fluorescence in situ hybridization (FISH) with the following panel of probes: 13q14/D13S25, 11q22/ATM, 17p13/TP53, #12-centromere and 14q32/IGH break-apart probe. CE was observed in 15/105 patients after 24-170 months (median 64). Recurring aberrations at CE were 14q32/IGH translocation in seven patients; other aberrations were 17p -, 11q -, biallelic 13q - and 14q32 deletion.

Chromosome 14q32 translocations involving the immunoglobulin heavy chain locus in chronic lymphocytic leukaemia identify a disease subset with poor prognosis.

Immunophenotypic studies, fluorescence in situ hybridization (FISH) and conventional karyotyping were used to define the clinicobiological significance of 14q32 translocations involving the immunoglobulin gene locus (14q32/IGH) in 252 chronic lymphocytic leukaemia (CLL) patients. The following regions were studied: 13q14, centromere 12, 6q21; 11q22/ATM; 17p13/TP53, 14q32/IGH. Patients were classified as group 1 (favourable, i.

Validation of an interphase fluorescence in situ hybridization approach for the detection of MLL gene rearrangements and of the MLL/AF9 fusion in acute myeloid leukemia.

To validate a 2-step FISH assay for the identification of the t(9;11)(p22;q23), 96 acute myeloid leukemias were studied by cytogenetic analysis, FISH and molecular biology. After a first FISH step using an MLL probe, 24/27 cases with 11q23 break showed MLL rearrangement. Southern blotting confirmed FISH data.

Abnormalities of chromosomes 1p34-36, 4p16, 4q35, 9q11-32 and +7 represent novel recurrent cytogenetic rearrangements in chronic lymphocytic leukemia.

Karyotypes were studied in over 250 cases of CLL seen at our Institution and 12 cases with a previously undescribed chromosome abnormality were identified. Cytogenetic and clinicobiological features in these patients are described. Fluorescence in situ hybridization using probes for the detection of +12 and deletions of 13q14, 17p13, and 11q22-23 was performed.

"In vitro" evaluation of bone marrow angiogenesis in myelodysplastic syndromes: a morphological and functional approach.

In myelodysplastic syndromes (MDS), ineffective hematopoiesis and cytopenia may arise either from increased susceptibility to apoptosis of hematopoietic cells, or possibly from alterations of bone marrow stroma that contributes to defective development of marrow lineages. In order to test the significance of the endothelial growth in MDS patients, two in vitro assays are presented in this study: a long-term culture method for the detection of human bone marrow endothelial colonies (CFU-En) (77 patients) and a human primary model for the evaluation of the influence of a "bone marrow conditioned medium" on the formation of new vessels in a culture matrix ("angio-kit assay") (in 24 out 77 patients). The in vitro growth pattern of bone marrow CFU-En as well as the generation of microvessels in the angio-kit system was increased in RA, RARS and RAEB in comparison with controls.

Late appearance of the 11q22.3-23.1 deletion involving the ATM locus in B-cell chronic lymphocytic leukemia and related disorders. Clinico-biological significance.

Background And Objectives: Chromosome 11q22.3-23.1 deletions involving the ataxia-teleangiectasia mutated (ATM) locus (11q-/ATM+/-) are detected at diagnosis in 10-20% of cases of B-cell chronic lymphocytic leukemia (CLL) and are associated with a relatively aggressive disease.