Immunophenotypic changes in juvenile myelomonocytic leukaemia after treatment with hypomethylating agent: Do they help to evaluate dept of response?

Abstract

Juvenile myelomonocytic leukaemia (JMML) is a rare clonal haematopoietic neoplasm from early childhood with characteristics of both myelodysplastic and myeloproliferative syndromes. It represents 3% of all haematologic malignancies in paediatric patients. [1][2][3] Most patients present mutation of genes of the Rat Sarcoma (RAS) pathway such as the genes tyrosine-protein phosphatase non-receptor type 11 (PTPN11), KRAS proto-oncogene, GTPase (KRAS), NRAS proto-oncogene, GTPase (NRAS), Casitas B-lineage lymphoma (CBL) and neurofibromin 1 (NF1). [4][5][6][7][8]

Phenotypic profiling of CD34⁺ cells by advanced flow cytometry improves diagnosis of juvenile myelomonocytic leukemia

“… 20-23 However, in contrast to other hematological malignancies, immunophenotyping is not part of the diagnostic work-up. Despite this, Oliveira et al have recently shown a significant decrease of T lymphocytes and the presence of several phenotypic abnormalities within CD34 + cells of JMML patients including the aberrant expression of CD7 in the majority of CD34 + CD117 + CD13 + cells, associated with a decrease or complete lack of CD19 + CD10 + B-cell precursors, 24 similarly to what has been described in adults with myelodysplastic syndrome (MDS) and/or myeloproliferative neoplasm (MPN). 25 , 26 …”

“…These aspects are currently being investigated and they may also contribute to a better understanding of the genetic heterogeneity of JMML patients. 24 , 26 , 39 …”

“…These aspects are currently being investigated and they may also contribute to a better understanding of the genetic heterogeneity of JMML patients. 24,26,39 However, given the limited sample size of our series and the possibility that RAS cases with lower scores could be RALD and not JMML, the power to assess phenotypic-genotypic associations should be considered with caution.…”

“…[20][21][22][23] However, in contrast to other hematological malignancies, immunophenotyping is not part of the diagnostic work-up. Despite this, Oliveira et al have recently shown a significant decrease of T lympho-cytes and the presence of several phenotypic abnormalities within CD34 + cells of JMML patients including the aberrant expression of CD7 in the majority of CD34 + CD117 + CD13 + cells, associated with a decrease or complete lack of CD19 + CD10 + B-cell precursors, 24 similarly to what has been described in adults with myelodysplastic syndrome (MDS) and/or myeloproliferative neoplasm (MPN). 25,26 Since 2012, the EuroFlow consortium has developed fully standardized approaches for immunophenotyping of hematological malignancies, including validated antibody panels, standardized sample preparation protocols, gating strategies and innovative (smart) data analysis and software tools embedded with artificial intelligence, to prospectively classify individual patients against a predefined reference database of normal/reactive and disease associated groups of subjects.…”