IGHV gene rearrangements as outcome predictors for CLL patients: Experience of Ukrainian group
National Cancer Institute, Kiev, Ukraine. Medical Oncology
(Impact Factor: 2.63).
03/2011; 29(2):1093-101. DOI: 10.1007/s12032-011-9872-5
Important characteristics of chronic lymphocytic leukaemia (CLL) cells are biased immunoglobulin variable heavy chain (IGHV) gene repertoire and expression of stereotyped B-cell receptors (BCRs); however, their prognostic value (in contrast to the impact of IGHV gene mutational status) is less clear. To evaluate the impact of separate IGHV gene usage and expression of stereotyped BCRs in CLL prognosis. Clinical data and IGHV gene configuration were analysed in 319 consecutive patients with CLL. We found that the majority of clinical parameters of patients were defined by IGHV mutational status. Our data also provided new evidence supporting the prognostic relevance of separate IGHV genes or stereotyped BCR in CLL, namely: (a) a restricted non-mutated (UM) IGHV gene repertoire in CLL patients with autoimmune haemolytic anaemia (AIHA) (more frequent expression of UM IGHV1-69, IGHV3-11 and IGHV4-59 genes, P = 0.001), a shorter period of AIHA development for expressors of these genes (P = 0.001) and a tendency towards expression of a stereotypic HCDR3 (P = 0.029), (b) a high incidence of second solid tumour development in IGHV3-21-expressing patients (P = 0.005) and (c) differences in overall survival (OS) of UM CLL patients depending on the BCR structure. Further research of specific IGHV gene usage and subsets of stereotyped BCRs in CLL may be helpful in more precise prediction of CLL prognosis in individual patients.
Available from: JA Hernández
- "Studies from Asia [21, 22], South America , and Europe [12, 26] showed a low representation of IGHV3-11 subfamily, with a similar proportion of M-CLL and U-CLL in this subgroup. However, the Ukrainian group showed that its presence was associated with an increased risk of developing autoimmune hemolytic anemia . Interestingly, in our cohort, IGHV3-11 gene was significantly overused in the unmutated group and was associated with a lower OS (P = 0.025), but we failed to find a relationship with the risk of developing autoimmune hemolytic anemia. "
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ABSTRACT: The aim of this study was to investigate the frequency and mutation status of the immunoglobulin heavy variable chain (IGHV) in a cohort of 224 patients from northwest and central region of Spain diagnosed with chronic lymphocytic leukemia (CLL), and to correlate it with cytogenetic abnormalities, overall survival (OS) and time to first treatment (TTFT). 125 patients had mutated IGHV, while 99 had unmutated IGHV. The most frequently used IGHV family was IGHV3, followed by IGHV1 and IGHV4. The regions IGHV3-30, IGHV1-69, IGHV3-23, and IGHV4-34 were the most commonly used. Only 3.1% of the patients belonged to the subfamily IGHV3-21 and we failed to demonstrate a worse clinical outcome in this subgroup. The IGHV4 family appeared more frequently with mutated pattern, similar to IGHV3-23 and IGHV3-74. By contrast, IGHV1-69 was expressed at a higher frequency in unmutated CLL patients. All the cases from IGHV3-11 and almost all from IGHV5-51 subfamily belonged to the group of unmutated CLL.
Available from: Andrey B. Sudarikov
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ABSTRACT: Abstract Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries including Israel, and is less frequent in the Orient, Asia and Middle Eastern Arabic speaking countries. These trends persist in migrants to other countries continuing into subsequent generations. Biological and genetic disparities have been reported for different ethnic groups. The absence of an association between place of birth and the occurrence of CLL is more in line with a genetic basis for the geographic variations in incidence. Genetic Abstpredisposition to CLL is supported by the documented familial aggregation of CLL with an increased frequency of 8.5 fold among first degree relatives of patients with CLL and the detection of CLL like clones in 13.5% of first degree relatives. It is likely that the development of chronic lymphocytic leukemia depends on the interplay of a genetic predisposition with exposure to environmental factors. To better understand the interplay of ethnicity and CLL we reviewed all the available literature on ethnic specific differences for this common form of leukemia.
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