Morphologic and Immunophenotypic Differences in Juvenile Myelomonocytic Leukemias with CBL and Other Canonical RAS-pathway Gene Mutations: A Single Institutional Experience

Rachel A. Mariani, Lawrence Jennings, Shanxiang Zhang, Rukhmi Bhat, Shunyou Gong*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The diagnostic criteria for juvenile myelomonocytic leukemia have recently been revised to include clinical findings and RAS-pathway gene mutations per the 2016 World Health Organization Classification of Tumors of Hematopoietic and Lymphoid Tissues. Differing clinical behaviors have been observed in cases with CBL versus other RAS-pathway gene (RAS-p) mutations, notably the patients with CBL mutations can be self-limiting with spontaneous resolution. Additional clinical characteristics and histopathologic findings between these subsets are less well-described. We performed a retrospective search and identified cases with either CBL or RAS-p mutations, as per targeted and/or massively parallel sequencing. Eight patients had sufficient material for review, including cytogenetic studies and peripheral blood, bone marrow aspirate, and/or biopsy with flow cytometry analyses. Three patients showed CBL mutations and lower percentages of hemoglobin F and peripheral blood absolute monocyte counts, lesser degrees of leukocytosis compared with the RAS-p cohort, and normal megakaryocyte morphology and myeloblast immunophenotypes. Two of these patients were managed with observation only and experienced resolution of their disease. The patients with RAS-p mutations had severe thrombocytopenia, moderate to severe anemia, and experienced variable clinical outcomes. Abnormal megakaryocyte morphology and decreased numbers of megakaryocytes were seen in cases with RAS-p mutations. In addition, 3 of 4 cases with flow cytometry data demonstrated aberrant CD7 expression in myeloblasts. Our study is the first to identify morphologic and immunophenotypic differences between juvenile myelomonocytic leukemia cases with CBL or RAS-p mutations, and further supports previous reports of significantly different clinical behaviors between these subsets of patients.

Original languageEnglish (US)
Pages (from-to)E819-E825
JournalJournal of pediatric hematology/oncology
Volume43
Issue number6
DOIs
StatePublished - Aug 2021
Externally publishedYes

Keywords

  • immunophenotype
  • Juvenile myelomonocytic leukemia
  • megakaryocyte

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

Fingerprint

Dive into the research topics of 'Morphologic and Immunophenotypic Differences in Juvenile Myelomonocytic Leukemias with CBL and Other Canonical RAS-pathway Gene Mutations: A Single Institutional Experience'. Together they form a unique fingerprint.

Cite this