Myelodysplastic and Myeloproliferative Subtypes of Chronic Myelomonocytic Leukemia Display Distinct Morphologic and Immunophenotypic Features
Leonardo Boiocchi, Nadia Di Lorenzo, Federica Savi, Anna Fargnoli, Attilio Orazi, Umberto Gianelli. Weill Cornell Medical College, New York, NY; Universita' di Milano, IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milano, Italy
Background: The distinction between myeloproliferative (MP) and myelodysplastic (MD) subtypes of chronic myelomonocytic leukemia (CMML) which is based on white blood cell count (WBC) of ≤ or >13x109/L has prognostic value, with MP-CMML being the more aggressive one. To date, very little characterization of bone marrow features of these two CMML subtypes has been reported.
Design: We studied 40 bone marrow biopsies (BMB) of CMML (14 MP and 26 MD). Ten staging BMB were used as normal controls (NC). H&E, reticulin and trichrome stains were used to evaluate morphology and fiber content. Immunohistochemistry for CD68R and CD14 was used to identify monocytes. CD34 was used to identify blasts and megakaryocytes (MK) aberrantly expressing this antigen. Hemoglobin, WBC, platelets, LDH and b2-microglobulin values were correlated with BMB findings. JAK2V617F and N-RAS and K-RAS mutational status was known in 15 cases (9 MP and 6 MD).
Results: MP-CMML in comparison to MD-CMML had, as expected, higher WBC (28.6 vs. 7.3x109/L; p<0.01), a lower number of lymphocytes (12.6 vs. 28.5x109/L), and increased LDH values (557 vs. 376 UI/L; p<0.01); b2-microglobulin did not show differences. BMB in MP-CMML in comparison with CMML-MD showed increased myeloid/erythroid ratio (p<0.05) due to myeloid proliferation and, in addition to dwarf hypolobulated forms seen in both subtypes, a higher number of large or giant MK with hyperlobulated nuclei. CD14 identified an increased number of monocytes in all CMML cases with higher values in MP- than in MD-CMML (p<0.003). No differences were noted in relation to the number of CD34 positive blasts. Of the cases with molecular results, 4 were mutated for RAS (2 MP and 2 MD) and 1 for JAK2V617F (1 MP). Among the RAS mutated cases, its presence was associated with a higher frequency of aberrant CD34 expression in MK (p=0.05), and higher LDH. The single JAK2 mutated case (MP-CMML) had slightly higher hemoglobin and platelet values than non-mutated MP cases.
Conclusions: There are important differences between the MD- and MP-CMML subtypes. In the latter, the BMB shows more numerous CD14 positive monocytes, more pronounced myeloid proliferation and more pleomorphic MK including large or giant cells with hyperlobulated nuclei. More frequent aberrant expression of CD34 in MK was found in association with RAS mutation. More studies will be needed to clarify molecular mechanisms causing heterogeneity in CMML and to identify clinically relevant correlates.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 230, Wednesday Morning