Molecular and phenotypic diversity of CBL-mutated juvenile myelomonocytic leukemia / Anna Hecht, Julia A. Meyer, Astrid Behnert, Eric Wong, Farid Chehab, Adam Olshen, Aaron Hechmer, Catherine Aftandilian, Rukhmi Bhat, Sung Won Choi, Satheesh Chonat, Jason E. Farrar, Mark Fluchel, Haydar Frangoul, Jennifer H. Han, Edward A. Kolb, Dennis J. Kuo, Margaret L. MacMillan, Luke Maese, Kelly W. Maloney, Aru Narendran, Benjamin Oshrine, Kirk R. Schultz, Maria L. Sulis, David Van Mater, Sarah K. Tasian, Wolf-Karsten Hofmann, Mignon L. Loh and Elliot Stieglitz
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..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
January, 2022 2022 |
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| Erschienen: |
January, 2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:107 |
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| Enthalten in: |
Haematologica - 107(2022), 1, Seite 178-186 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hecht, Anna, 1986- [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Pre-published: December 30, 2020 Gesehen am 22.02.2022 |
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| Umfang: |
9 |
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| doi: |
10.3324/haematol.2020.270595 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Molecular and phenotypic diversity of CBL-mutated juvenile myelomonocytic leukemia |c Anna Hecht, Julia A. Meyer, Astrid Behnert, Eric Wong, Farid Chehab, Adam Olshen, Aaron Hechmer, Catherine Aftandilian, Rukhmi Bhat, Sung Won Choi, Satheesh Chonat, Jason E. Farrar, Mark Fluchel, Haydar Frangoul, Jennifer H. Han, Edward A. Kolb, Dennis J. Kuo, Margaret L. MacMillan, Luke Maese, Kelly W. Maloney, Aru Narendran, Benjamin Oshrine, Kirk R. Schultz, Maria L. Sulis, David Van Mater, Sarah K. Tasian, Wolf-Karsten Hofmann, Mignon L. Loh and Elliot Stieglitz |
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| 520 | |a 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. | ||
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