Association of the prognostic leukemic cell surface markers with the mutation status of the immunoglobulin heavy chain variable region genes in untreated patients with chronic lymphocytic leukemia.

Objectives. Chronic lymphocytic leukemia (CLL), the most common type of adult leukemia, shows highly variable disease courses. Patients with the low-risk disease do not require chemoimmunotherapies, while patients with the high-risk CLL need the therapy urgently. The mutation status of the immunoglobulin heavy chain variable region genes (IGHV) is currently determining the choice for therapy in CLL. CD38 expression on circulating CLL cells had been associated with the unmutated IGHV. Earlier, we demonstrated in CLL patients the correlation between expression on PB CD19+CD5+ lymphocytes of CD38 and the chemokine receptors CCR1 and CCR2. Since mutation analyses are still unavailable to many CLL patients due to the complexity and expenses, we analyzed an association of the IGHV mutation status with the coexpression
of the cell-surface markers CD38, CCR1, and CCR2, which can be used in the routine clinical flow cytometry (FC) diagnostic.
Materials and Methods. We determined the IGHV mutation rates in 100 untreated CLL patients using the European Research Initiative on CLL (ERIC) recommendations and protocol. The frequencies of the CD38-, CCR1-, and CCR2-expressing PB CD19+CD5+ lymphocytes were measured using multiparameter flow cytometry. The study was funded by the projects: LZP No.lzp-2018/1-0156 and RSU Nr.6-ZD-22/14/2022.
Results. The frequency of the CCR1- and CCR2-expressing PB CD19+CD5+ lymphocytes in untreated CLL patients positively correlated with the frequency of the known negative prognostic marker CD38. Higher frequencies of the CD38-expressing (> 30%) and CCR2-expressing (> 10%) PB CD19+CD5+ lymphocytes were observed in patients with unmutated IGHV: 33% and 70%, respectively, versus 20% and 52% in patients with mutated IGHV.
Conclusions. Migration of the CCR2-expressing CLL cells into secondary lymphoid organs apparently contribute to disease progression. Along with CD38, detection of CCR1 and CCR2 on circulating leukemic cells can be suggested for the clinical FC diagnostic to assure accurate prognoses of the high-risk progression in C LL.