Perspectives on the Application of Cytogenomic Approaches in Chronic Lymphocytic Leukaemia

Abstract

Chronic lymphocytic leukaemia (CLL) is a haematological malignancy characterised by the accumulation of monoclonal mature B lymphocytes (positive for CD5+ and CD23+) in peripheral blood, bone marrow, and lymph nodes. Although CLL is reported to be rare in Asian countries compared to Western countries, the disease course is more aggressive in Asian countries than in their Western counterparts. It has been postulated that this is due to genetic variants between populations. Various cytogenomic methods, either of the traditional type (conventional cytogenetics or fluorescence in situ hybridisation (FISH)) or using more advanced technology such as DNA microarrays, next generation sequencing (NGS), or genome wide association studies (GWAS), were used to detect chromosomal aberrations in CLL. Up until now, conventional cytogenetic analysis remained the gold standard in diagnosing chromosomal abnormality in haematological malignancy including CLL, even though it is tedious and time-consuming. In concordance with technological advancement, DNA microarrays are gaining popularity among clinicians as they are faster and better able to accurately diagnose the presence of chromosomal abnormalities. However, every technology has challenges to overcome. In this review, CLL and its genetic abnormalities will be discussed, as well as the application of microarray technology as a diagnostic platform.

The role of polymorphic cytochrome P450 gene (CYP2B6) in B-chronic lymphocytic leukemia (B-CLL) incidence and outcome among Egyptian patients

“…Cytogenetic analysis is useful for identifying certain chromosomal abnormalities that affect the disease’s prognosis and could affect the choice of treatment [ 33 ]. We observed that 1%, 18%, 4% and 1% of patients, respectively, had 13q14 del, 11q23 del, 17p13 del and trisomy.…”

Adaptive and Innate Cytotoxic Effectors in Chronic Lymphocytic Leukaemia (CLL) Subjects with Stable Disease

“…Stable CLL could be considered as a peculiar case of a long-term equilibrium between the clonally transformed B-cell population and immune-mediated antineoplastic activity. For the comparative analysis of CD54 expression on T lymphocytes as well as of HLA-I and APM molecule expression in B and T cells, immune-fluorescence data were expressed as ratio of mean intensity fluorescence (MIF) value for each lymphocyte subset and the control MIF value obtained after staining the same cell population with the isotype control mAb, as described [5,52].…”

“…In this context, early stage asymptomatic patients show partial long-term benefits or no therapeutic effect from early drug treatment, while patients with advanced disease necessarily require first-line therapy to limit disease progression [1][2][3]. Several alterations, such as p53 mutation, immunoglobulin heavy-chain variable gene (IGHV) mutational status, cytogenetic and epigenetic modification [4][5][6], as well as micro-environmental stimulation [7], have been proposed as predictive and/or diagnostic biomarkers of the disease. However, the need for additional disease markers is recognised as essential to improve the diagnostic and predictive criteria of CLL disease.…”

“…We recently described that T R3-56 , co-expressing CD3 and CD56 molecules, represents a peculiar human regulatory T-cell subset, phenotypically, metabolically and genetically distinct from NKT subset [50,51]. T R3-56 subset is preferentially involved in the control of cytotoxic activity and in the production of IFN-γ by cytotoxic T cells [5,51]. T R3-56 cells are significantly reduced in type 1 diabetes (T1D) at disease onset [51] and are inversely correlated with the presence of activated cytotoxic T lymphocytes with a skewed Vβ T-cell repertoire in the bone marrow (BM) of myelodysplastic subjects [52].…”