Clinical management of three JMML siblings with germline CBL variation

Cancer Genet. 2025 Apr:292-293:120-123. doi: 10.1016/j.cancergen.2025.02.007. Epub 2025 Feb 19.

Abstract

Germline pathogenic variants (PVs) in CBL are found in 15 % of juvenile myelomonocytic leukemia (JMML) cases. Here we report three siblings with CBL(NM_005188):c.1111T>C variation presenting a heterogenous JMML clinic and outcome. The index case was diagnosed at the age of seven, whereas the younger brother was 10 months old and the youngest was one month old. The hematopoietic stem cell transplantation was successful for the index and the youngest brother with event-free survival, but the middle brother showed severe graft versus host disease. This study shows the heterogeneity of JMML and how the outcome might differ even within the family.

Keywords: CBL; Hematopoietic stem cell transplantation; Juvenile myelomonocytic leukemia.

Publication types

  • Case Reports

MeSH terms

  • Child
  • Female
  • Germ-Line Mutation*
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Infant
  • Leukemia, Myelomonocytic, Juvenile* / genetics
  • Leukemia, Myelomonocytic, Juvenile* / pathology
  • Leukemia, Myelomonocytic, Juvenile* / therapy
  • Male
  • Proto-Oncogene Proteins c-cbl* / genetics
  • Siblings

Substances

  • Proto-Oncogene Proteins c-cbl
  • CBL protein, human