Immunopathogenesis and SETBP1 mutation analysis in chronic myelomonocytic leukemia

To assess the diagnostic value of peripheral blood (PB) and bone marrow (BM) smears, SETBP1 gene mutation analysis, and bone marrow trephine biopsy (BMTB) histology, supplemented by immunohistochemistry in distinguishing chronic myelomonocytic leukemia (CMML) from chronic myeloid leukemia (CML) (chronic phase) and acute monocytic leukemia (AMoL). PB and BM smears were analyzed in 51 CMML patients. Immunostaining of myeloid- and monocyte-specific markers in 26 CMML patients was compared that observed in 30 CML patients and 30 AMoL patients. SETBP1 mutations were investigated in 28 CMML patients. Most CMML patients presented with leukocytosis (median WBC count, 41.90 +/- 36.70x10(9)/l) with marked monocytosis (median: CMML-1, 5.04 +/- 3.90x10(9)/l; CMML-2, 10.63 +/- 11.60x10(9)/l). BM smears were hypercellular in 44 patients, with increased in granulocytic proliferation and monocytes numbers. In BMTB, CMML was characterized as hypercellular in 84.6% patients, with a moderate degree of monocytosis (76.9%). Approximately 34.6% of patients had slightly increased BM fibrosis. Positive immunoreactivity in CMML patients was as follows: MPO, 33.82 +/- 6.83%; CD15, 21.97 +/- 7.15%; CD34, 4.44 +/- 1.98%; CD117, 1.35 +/- 0.57%). Monocytic markers, such as CD14, CD56, CD68 (PG-M1) and CD163 were positive in mean 10.30 +/- 2.55%, 8.61 +/- 2.99%, 13.24 +/- 4.64% and 10.50 +/- 4.21% of positive cells, respectively. No SETBP1 mutations were detected in 28 CMML patients. Morphological and immunohistochemical features of BMTB samples combined with analysis of PB and BM smears are helpful in distinguishing CMML from CML and AMoL.