HLA Gene Polymorphisms in Romanian Patients with Chronic Lymphocytic Leukemia

Area of Science:

• Immunogenetics
• Oncology
• Human Genetics

Background:

• Chronic lymphocytic leukemia (CLL) is a heterogeneous hematologic malignancy.
• The human leukocyte antigen (HLA) system plays a crucial role in immune response and has been implicated in various diseases.
• Understanding the genetic associations of HLA alleles with CLL can provide insights into disease pathogenesis and potential therapeutic targets.

Purpose of the Study:

• To investigate the association between specific human leukocyte antigen (HLA) class I and class II alleles and the risk of developing chronic lymphocytic leukemia (CLL) in a Romanian population.
• To identify HLA alleles that may predispose to or protect against CLL development.

Main Methods:

• Next-generation sequencing was employed to analyze HLA class I (HLA-A/B/C) and class II (HLA-DQA1/DQB1/DPA1/DPB1, HLA-DRB1/3/4/5) genes.
• The study included 66 patients diagnosed with CLL between 2020 and 2022 and 100 healthy controls.

Main Results:

• Several HLA alleles showed significant associations with CLL.
• HLA-DRB1*04:02:01 and HLA-DRB3*02:01:01 were identified as predisposing alleles for CLL development (p=0.001, OR=1.05; p=0.009, OR=1.03, respectively).
• Protective alleles against CLL included HLA-A*24:02:01 (p=0.01, OR=0.38), HLA-DQA1*05:05:01 (p=0.01, OR=0.56), HLA-DQB1*03:02:01 (p=0.03, OR=0.40), and HLA-DRB4*01:03:01 (p=0.03, OR=0.54).
• Women exhibited higher expression of protective HLA alleles compared to men.

Conclusions:

• This study provides the first evidence in Romanian patients that HLA-A*24:02:01 and HLA-DQA1*05:05:01 alleles are protective against CLL development.
• Conversely, HLA-DRB1*04:02:01 and HLA-DRB3*02:01:01 alleles are positively associated with an increased risk of CLL.
• These findings highlight the role of specific HLA alleles in CLL susceptibility and warrant further investigation into their functional implications.