NG2 MOLECULE EXPRESSION IN ACUTE LYMPHOBLASTIC LEUKEMIA B CELLS: A FLOW-CYTOMETRIC MARKER FOR THE RAPID IDENTIFICATION OF KMT2A GENE REARRANGEMENTS

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Maria Laura Bisegna
Nadia Peragine
Loredana Elia
Mabel Matarazzo
Maria Laura Milani
Stefania Intoppa
Mariangela Di Trani
Francesco Malfona
Maurizio Martelli
Maria Stefania De Propris

Keywords

NG2, flow-cytometry, acute lymphoblastic leukemia, KMT2A gene rearrangements

Abstract


Background: B-lineage acute lymphoblastic leukemias (B-ALL) harboring rearrangements of the histone lysine [K]-Methyltransferase 2A (KMT2A) gene on chromosome 11q23 (KMT2A-r), represent a category with dismal prognosis. The prompt identification of these cases represents an urgent clinical need. Considering the correlation between rat neuron glial-antigen 2 (NG2) chondroitin sulfate proteoglycan molecule expression and KMT2A-r, we aimed identifying an optimized cytofluorimetric diagnostic panel to predict the presence of KMT2A-r.                                                                                                                                           Materials and Methods: We evaluated 88 NG2+ B-ALL cases identified with a NG2 positivity threshold >10%, from a cohort of 1382 newly diagnosed B-ALLs referred to the Division of Hematology of ‘Sapienza’ University of Rome.                                                       Results: Eighty-five of 88 (96.6%) NG2+ B-ALLs harbored KMT2A-r and were mainly pro-B ALL (77/85; 91%). Only 2 B-ALLs with KMT2A-r showed NG2 expression below 10%, probably due to the steroid therapy administered prior to cytofluorimetric analysis. When compared to KMT2A-r‒ cases, KMT2A r+ B-ALLs presented a higher blast percentage, a significantly higher mean fluorescence intensity (MFI) of CD45, CD38 and CD58, and a significantly lower CD34, CD22, TdT and CD123 MFI. The differences in CD45, CD34, CD22 and TdT MFI were confirmed within the same immunologic EGIL (European Group for the immunological classification of leukemias) group, suggesting no influence of the B-ALLs EGIL subtype on the peculiar KMT2A-r+ B-ALLs immunophenotype. Conclusions: Our data show how the association between NG2 and KMT2A-r in B-ALLs identify a peculiar immunophenotypic pattern, useful for rapid identification in diagnostic routines of these subtypes of B-ALLs with a poor prognosis, that benefit from a specific therapeutic approach.


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