Acute Monoblastic/Monocytic Leukemia and Chronic Myelomonocytic Leukemia Share Common Immunophenotypic Features but Differ in the Extend of Aberrantly Expressed Antigens and the Amount of Granulocytic Cells.
Authors: Kern Wolfgang , Haferlach Claudia , Schnittger Susanne , Haferlach Torsten 
Published: October 2019

Abstract 3799
Poster Board III-735
Acute monoblastic/monocytic leukemia (AMoL) is grouped into acute myeloid leukemia and related neoplasms by the 2008 WHO classification while chronic myelomonocytic leukemia (CMML) in grouped into myelodysplastic/myeloproliferative neoplasms (MDS/MPN). However, both entities share common features and sometimes may be difficult to differentiate from each other. In particular, monopoietic cells can be easily identified by multiparameter flow cytometry (MFC) based on their CD45/side-scatter (SSC) signal. However, immunophenotypes of monoblasts and dysplastic monocytes largely overlap. Their differentiation from each other is better accomplished by cytomorphology (CM) and the use of non-specific esterase. We compared cytomorphologic, immunophenotypic and cytogenetic results between 26 patients with AMoL and 139 patients with CMML which were analyzed at diagnosis between 2005 and 2009 in order to identify shared and discriminative characteristics. In AMoL vs. CMML 65.4% vs. 73.4% were male, the median age was 65.4 vs. 72.5 years (range 19.3-82.0 vs. 21.9-87.9 years, p<0.001), and the median WBC count was 38.0 G/L vs. 10.4 G/l (range 0.8-126.0 G/l vs. 0.9-92.0 G/l, p<0.001). Cytogenetics differed in that a normal karyotype was found in 79.1% of CMML cases and in only 38.5% of AMoL cases (p<0.0001). Per definition, a t(9;11) (19.2%) was found only in AMoL (p<0.001) which was almost identical for other translocations involving MLL (15.4% vs. 0.7%, p=0.003). Other cytogenetic abnormalities did not significantly differ between AMoL and CMML. First, immunophenotypes of monopoietic cells were compared between AMoL and CMML. While an aberrant coexpression of CD56 was present in all cases with AMoL this was true in only 82.0% of CMML cases (p=0.015). No other aberrantly expressed antigen was found in AMoL while in CMML a coexpression of CD2 was found in 21.6% (p=0.005), a lack of CD13 expression in 10.8% (n.s.), and a lack of HLA-DR expression in 4.3% (n.s.). Next, we compared the frequencies of different cell types between AMoL and CMML as identified by CM and MFC. In this analysis, granulocytic cells by CM included cells of all maturation grades from promyelocyte to granulocyte, which corresponds to the population identified in MFC by their dim expression of CD45 and their strong SSC signal. As anticipated when considering the definition of the respective entities CM identified higher percentages of blasts (mean±SD 78.7±13.8 vs. 8.6±5.1, p<0.001) and lower percentages of monocytes (1.7±3.9 vs. 13.8±11.9, p<0.001) and granulocytic cells (7.9±7.4 vs. 53.8±15.8, p<0.001) in AMoL vs. CMML. Applying the blast gate in the CD45/side-scatter analysis for the identification of blasts (CD45(+)SSC-) MFC also found higher percentages of blasts in AMoL vs. CMML (18.2±25.1 vs. 4.0±3.2, p<0.001) and monopoietic cells were found also at higher frequencies in AMoL (28.6±27.4 vs. 20.1±12.3, p=0.012). Interestingly, however, MFC identified significantly higher frequencies of granulocytic cells in CMML (52.2±19.3 vs. 26.2±22.6, p<0.001). Thus, while the CD45-SSC analysis is not capable of differentiating between monocytes and monoblasts it may be used to identify high percentages of granulocytic cells which is characteristic for CMML but not for AMoL. Based on these findings, the ratio M:G (monopoietic cells:granulocytic cells) was calculated for each case. The ratio M:G was significantly higher in AMoL as compared to CMML (mean±SD 5.2±10.4 vs. 0.8±2.3, p<0.001). In conclusion, the present data demonstrate that AMoL and CMML after being discriminated according to WHO guidelines for cytomorphology share common features as identified by MFC but differ in the extend of aberrantly expressed antigens and the amount of granulocytic cells. For further studies and to support CM these parameters should be evaluated when using MFC as a diagnostic tool for AMoL and CMML.

Disclosures:
Kern: MLL Munich Leukemia Laboratory: Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Equity Ownership. Schnittger:MLL Munich Leukemia Laboratory: Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Equity Ownership.