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Molecular and phenotypic diversity of CBL-mutated juvenile myelomonocytic leukemia
- Source :
- Haematologica. 107:178-186
- Publication Year :
- 2020
- Publisher :
- Ferrata Storti Foundation (Haematologica), 2020.
-
Abstract
- Mutations in the CBL gene 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 patients with 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 that this disease is 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 patients with somatic CBL mutations from those with germline CBL mutations, highlighting the need for germline testing. Overall, we demonstrate that disease courses are quite heterogeneous even among patients with germline CBL mutations. Prospective clinical trials are warranted to find ideal treatment strategies for this diverse cohort of patients.
- Subjects :
- 0303 health sciences
Myeloid
Juvenile myelomonocytic leukemia
business.industry
Somatic cell
Hematology
Disease
medicine.disease
Phenotype
Uniparental disomy
Germline
03 medical and health sciences
0302 clinical medicine
medicine.anatomical_structure
hemic and lymphatic diseases
030220 oncology & carcinogenesis
medicine
Cancer research
business
Gene
030304 developmental biology
Subjects
Details
- ISSN :
- 15928721 and 03906078
- Volume :
- 107
- Database :
- OpenAIRE
- Journal :
- Haematologica
- Accession number :
- edsair.doi...........092f2aed67158eda9c89ea67f834bc56