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Molecular and phenotypic diversity of CBL-mutated juvenile myelomonocytic leukemia.

Publication ,  Journal Article
Hecht, A; Meyer, JA; Behnert, A; Wong, E; Chehab, F; Olshen, A; Hechmer, A; Aftandilian, C; Bhat, R; Choi, SW; Chonat, S; Farrar, JE; Han, JH ...
Published in: Haematologica
January 1, 2022

Mutations in the gene CBL were first identified in adults with various myeloid malignancies. Some patients with juvenile myelomonocytic leukemia (JMML) were also noted to harbor mutations in CBL, but were found to have generally less aggressive disease courses compared to other forms of Ras pathway-mutant JMML. Importantly, and in contrast to most reports in adults, the majority of CBL mutations in JMML patients are germline with acquired uniparental disomy occurring in affected marrow cells. Here, we systematically studied a large cohort of 33 JMML patients with CBL mutations and found this disease to be highly diverse in presentation and overall outcome. Moreover, we discovered somatically-acquired CBL mutations in 15% of pediatric patients who presented with more aggressive disease. Neither clinical features nor methylation profiling were able to distinguish somatic CBL patients from germline CBL patients, highlighting the need for germline testing. Overall, we demonstrate that disease courses are quite heterogeneous even among germline CBL patients. Prospective clinical trials are warranted to find ideal treatment strategies for this diverse cohort of patients.

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Published In

Haematologica

DOI

EISSN

1592-8721

Publication Date

January 1, 2022

Volume

107

Issue

1

Start / End Page

178 / 186

Location

Italy

Related Subject Headings

  • Proto-Oncogene Proteins c-cbl
  • Prospective Studies
  • Mutation
  • Leukemia, Myelomonocytic, Juvenile
  • Immunology
  • Humans
  • Child
  • Adult
  • 3201 Cardiovascular medicine and haematology
  • 1102 Cardiorespiratory Medicine and Haematology
 

Citation

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Hecht, A., Meyer, J. A., Behnert, A., Wong, E., Chehab, F., Olshen, A., … Stieglitz, E. (2022). Molecular and phenotypic diversity of CBL-mutated juvenile myelomonocytic leukemia. Haematologica, 107(1), 178–186. https://doi.org/10.3324/haematol.2020.270595
Hecht, Anna, Julia A. Meyer, Astrid Behnert, Eric Wong, Farid Chehab, Adam Olshen, Aaron Hechmer, et al. “Molecular and phenotypic diversity of CBL-mutated juvenile myelomonocytic leukemia.Haematologica 107, no. 1 (January 1, 2022): 178–86. https://doi.org/10.3324/haematol.2020.270595.
Hecht A, Meyer JA, Behnert A, Wong E, Chehab F, Olshen A, et al. Molecular and phenotypic diversity of CBL-mutated juvenile myelomonocytic leukemia. Haematologica. 2022 Jan 1;107(1):178–86.
Hecht, Anna, et al. “Molecular and phenotypic diversity of CBL-mutated juvenile myelomonocytic leukemia.Haematologica, vol. 107, no. 1, Jan. 2022, pp. 178–86. Pubmed, doi:10.3324/haematol.2020.270595.
Hecht A, Meyer JA, Behnert A, Wong E, Chehab F, Olshen A, Hechmer A, Aftandilian C, Bhat R, Choi SW, Chonat S, Farrar JE, Fluchel M, Frangoul H, Han JH, Kolb EA, Kuo DJ, MacMillan ML, Maese L, Maloney KW, Narendran A, Oshrine B, Schultz KR, Sulis ML, Van Mater D, Tasian SK, Hofmann W-K, Loh ML, Stieglitz E. Molecular and phenotypic diversity of CBL-mutated juvenile myelomonocytic leukemia. Haematologica. 2022 Jan 1;107(1):178–186.

Published In

Haematologica

DOI

EISSN

1592-8721

Publication Date

January 1, 2022

Volume

107

Issue

1

Start / End Page

178 / 186

Location

Italy

Related Subject Headings

  • Proto-Oncogene Proteins c-cbl
  • Prospective Studies
  • Mutation
  • Leukemia, Myelomonocytic, Juvenile
  • Immunology
  • Humans
  • Child
  • Adult
  • 3201 Cardiovascular medicine and haematology
  • 1102 Cardiorespiratory Medicine and Haematology