Background. Chronic lymphocytic leukemia (CLL), the most common adult leukemia, arises from clonal expansion of dysfunctional CD5+ B lymphocytes and remains incurable despite modern targeted therapy. A central feature is active remodeling of the tumor microenvironment, which sustains leukemic survival and shields the clone from immune clearance. Methods. This study profiled the coordinated expression of three chemokines (CCL3, CCL4, CCL5), β2- microglobulin (B2M), and five B-cell differentiation transcription factors in peripheral blood B-lymphocytes from 34 CLL patients versus age-matched healthy donors, using RT-qPCR and the 2^−ΔΔCt method. Results. CCL3 (MIP-1α) and CCL4 (MIP-1β) were significantly upregulated, consistent with tonic and antigen-driven BCR-NF-κB signaling. Via CCR1/CCR5 they recruit T-regulatory and nurselike cells that deliver pro-survival signals (APRIL, BAFF, IL-6), confirming active immunosuppressive niche construction. In contrast, CCL5 and B2M were downregulated. Reduced CCL5 — primarily a T/NK-cell product — reflects impaired cytotoxic recruitment and T-cell exhaustion, while B2M loss compromises MHC class I surface display and antigen presentation. Together they form a dual immune-evasion mechanism: diminished effector recruitment and reduced target recognition. A hierarchically graded suppression of differentiation transcription factors was observed (2- to 15.5-fold). The earliest-acting regulators were most affected — EBF1 (15.5-fold) and PU.1 (14-fold) — indicating dismantling of core B-lineage identity. BLIMP1 (4-fold) explains the block in terminal plasma-cell maturation, while IRF8 (3.5-fold) and IRF4 (2-fold) consolidate arrest at intermediate stages. The gradient — deepest at progenitor-commitment factors and milder downstream — suggests the transcriptional block acts most forcefully on B-lineage identity itself, favoring sustained self-renewal over terminal maturation. Conclusions. CLL B-lymphocytes run a coordinated, mechanistically linked dual program of immune evasion and differentiation arrest. The CCL3/CCL4–CCR5 pathway (targetable by repurposed CCR5 antagonists), B2M loss (relevant to CAR-T responsiveness), and EBF1/PU.1 restoration as a differentiation-induction strategy emerge as actionable therapeutic directions. Fundings. Supported by NRFU grant No. 0124U003787, “Activation of signaling cascades for elimination of transformed B-cells in CLL”.