Chronic Lymphocytic Leukemia: Causes

Pathogenesis (disease development)

Chronic lymphocytic leukemia (CLL) is due to malignant transformation of a B-cell clone in 95% of cases. It is considered a leukemic B-cell lymphoma. It involves mature, small-cell but non-functional B lymphocytes (B cells; they belong to the leukocytes (white blood cells); they are the only cells capable of producing antibodies; together with T lymphocytes, they make up the crucial component of the adaptive immune system) that occur en masse in the peripheral blood.*

* In addition to CLL, the WHO classification distinguishes another subtype, “small lymphocytic lymphoma” (B-SLL, small B-cell lymphoma), which is essentially equivalent to CLL in which lymph node involvement is entirely prominent without leukemia (in a sense, a non-leukemic CLL).

Etiology (causes)

Biographic causes

  • Genetic burden – first-degree relatives of CLL patients have an 8.5-fold increased risk of developing CLL and a 1.9-2.6-fold increased risk of developing another indolent lymphoma
    • Genetic risk dependent on gene polymorphisms:
      • Genes/SNPs (single nucleotide polymorphism):
        • Genes: ACOXL, GRAMD1B, IRF4, SP140.
        • SNP: rs735665 in the GRAMD1B gene.
          • Allele constellation: AG (1.45-fold).
          • Allele constellation: AA (2.10-fold)
        • SNP: rs13397985 in gene SP140
          • Allele constellation: GT (1.41-fold).
          • Allele constellation: GG (1.99-fold)
        • SNP: rs17483466 in the gene ACOXL.
          • Allele constellation: AG (1.39-fold).
          • Allele constellation: GG (1.93-fold)
        • SNP: rs7176508 in an intergenic region.
          • Allele constellation: AG (1.37-fold).
          • Allele constellation: AA (1.88-fold)
        • SNP: rs872071 in the gene IRF4
          • Allele constellation: AG (1.5-fold)
          • Allele constellation: GG (1.5-fold)

Behavioral causes