Prognostic markers of disease progression in untreated patients with chronic lymphocytic leukemia

Recently updated guideline recommendations by the National Comprehensive Cancer Network (NCCN) and the CLL International Prognostic Index (CLL-IPI) include host factors (gender, age, lymphocytosis, lymphadenopathy, splenomegaly, thrombocytosis, hemoglobin level), disease staging (Rai and Binet), serology (lactate dehydrogenase, beta-2-microglobulin, and thymidine kinase), genetics (TP53 and NOTCH1 genes mutation status), immunogenetics (immunoglobulin heavy chain variable region [IGHV] gene mutational status), and phenotype of leukemic cells (CD38, ZAP70, CD200, and CD49d/VLA-4). The precise value of these markers for prognosis of disease progression in naïve CLL patients remains in question. A simplified prognostic index applicable in naïve CLL is required. Peripheral blood (PB) lymphocytes of 61 newly diagnosed CLL patients were analyzed by polychromatic flow cytometry (pFC) for expression of the CLL-specific markers (CD19, CD5, CD23), the known negative prognostic marker CD38, and the chemokine receptors CCR1 and CCR2. ZAP70 mRNA expression levels and the IGHV gene mutational status were assessed. Rai staging and host factors were also included in Spearman’s rank correlation analyses. Out of 61 CLL patients, 39 were CD38-positive and 22 were CD38-negative. CCR1 and/or CCR2 were always expressed on the PB CD19+CD5+ lymphocytes in patients with >30% of the CD38+ leukemic cells (n = 16). Spearman’s rank correlation analysis defined correlations between the frequency of the CCR1/CCR2 and CD38 on PB CD19+CD5+ lymphocytes (r = 0.50 and r = 0.38, respectively). Unmutated IGHV gene was detected as in CD38-positive as in CD38-negative patients. No significant correlations were determined between ZAP70 mRNA expression levels and the frequency of the CCR1+ or CCR2+ CD19+CD5+ lymphocytes. CCR1/CCR2 on the PB CD19+CD5+ lymphocytes could be suggested as additional prognostic markers applicable in routine clinical FC tests for diagnosis of the high-risk CLL patients. The studies were funded by the Latvian Council of Science projects No.651/2014 and No.lzp-2018/1-0156.