Chronic lymphocytic leukemia (CLL) is the most frequent type of leukemia in adults in the Western hemisphere, with an annual incidence of 4.7 cases per 100 000 inhabitants according to the Surveillance, Epidemiology and End Results (SEER) Program and mean age at diagnosis of 70 years.^1,2 CLL is a hematologic malignancy characterized by the proliferation of mature monoclonal B lymphocytes, often preceded by the subclinical stage of monoclonal B‑cell lymphocytosis. Malignant clone accumulates in the blood, bone marrow, and lymphatic tissue. CLL diagnosis is confirmed by the presence of at least 5000 B cells/µl in the peripheral blood for at least 3 months.² While many patients are asymptomatic and do not require upfront treatment, symptomatic or active disease therapy should be initiated according to the defined criteria.² Recent progress in CLL therapy has resulted in a plethora of treatment choices, providing hematologists with a broader array of effective strategies. However, there are still many questions as to which therapeutic options are the most suitable for specific patients to ultimately cure CLL.

The answers may be hidden in the specific biology of CLL, which strongly relies on the microenvironment. It plays a crucial role in protecting the malignant B‑cell clone from apoptosis and promoting the survival and proliferation of leukemia. Key players of the microenvironment include different types of immunocompetent cells, including stromal cells, nurse‑like cells, monocytes, and T lymphocytes, which interact with CLL cells through various adhesion molecules, chemokine receptors, and soluble factors.³

In this issue of Polish Archives of Internal Medicine, Kosmaczewska et al⁴ addressed the role of T cells in the survival of CLL cells, focusing on the expression of key players controlling G1 phase of the cell cycle, namely p27^Kip1 and cyclin D2, in both malignant B cells and nonmalignant T cells. By employing flow cytometry, the authors analyzed the expression of these critical regulators of the cell cycle in the cells isolated from a cohort of 47 previously untreated CLL patients and the healthy controls. Additionally, the apoptosis rate was assessed in both types of lymphocytes.

Median follow‑up was 116.8 (19–288) months. The authors linked the higher expression of cell cycle inhibitor p27^Kip1 and the lower expression of cyclin D2 to early disease progression, which points to a potentially ambiguous role of the key cell cycle regulators in CLL biology and warrants further studies.

Interestingly, the rate of apoptosis was highest in nonmalignant T cells from the CLL patients, when compared with both T cells from the healthy participants and B leukemic cells. This confirms previous studies implicating a significant role of T cells in the pathogenesis of CLL and deregulation of the immune system in CLL patients.

Results presented by Kosmaczewska et al⁴ are a perfect example of a complex pathogenesis of CLL, a disease which cannot be fully understood when considered just as simple B‑cell monoclonal malignancy.