Chronic lymphocytic leukemia cell (CLL cell)

Chronic lymphocytic leukemia (CLL) cells are monoclonal, mature-appearing B-lymphocytes that progressively accumulate in the peripheral blood, bone marrow, and lymphoid tissues [1, 13]. These malignant cells are characterized by a distinct immunophenotype, typically co-expressing CD5, CD19, and CD23 [13]. A hallmark of CLL cells is their ability to evade apoptosis through the overexpression of the anti-apoptotic protein B-cell lymphoma 2 (BCL-2), despite often having low proliferative rates [2, 13]. Their survival and expansion are also heavily dependent on constitutive signaling through the B-cell receptor (BCR) pathway, which involves critical kinases such as Bruton's tyrosine kinase (BTK) and phosphoinositide 3-kinase (PI3K) delta [1, 14]. Therapeutic management involves targeting these cells with small molecule inhibitors like ibrutinib (BTK inhibitor) and venetoclax (BCL-2 inhibitor), or monoclonal antibodies like rituximab that target surface antigens such as CD20 [4, 5, 15]. Elimination of these cells is the primary objective in treating chronic lymphocytic leukemia and small lymphocytic lymphoma [7].

Other names

CLL B-cellB-cell chronic lymphocytic leukemia cellMalignant B-lymphocyteMonoclonal B-lymphocyte

Drugs targeting CLL cells primarily act through the inhibition of critical survival pathways, including the B-cell receptor signaling cascade via Bruton's tyrosine kinase (BTK) and phosphoinositide 3-kinase (PI3K) inhibitors, as well as the antagonism of anti-apoptotic proteins like BCL-2 [1, 2, 4]. Additionally, monoclonal antibodies directed against surface antigens such as CD20 induce cell death through antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) [5, 15].