Development of Philadelphia chromosome-negative acute myeloid leukemia with IDH2 and NPM1 mutations in a patient with chronic myeloid leukemia who showed a major molecular response to tyrosine kinase inhibitor therapy
| Autor: | Hiroko Tanaka, Kinuko Mitani, Fusako Nagasawa, Satoru Miyano, Yuko Nakamura, Shiho Furuichi, Tomoyuki Handa, Fumi Nakamura, Yasuhito Nannya, Wataru Takahashi, Honoka Arai, Motoshi Ichikawa, Ko Sasaki, Seishi Ogawa, Yuka Nakamura |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
medicine.medical_specialty NPM1 medicine.drug_class Population Dasatinib Tyrosine-kinase inhibitor 03 medical and health sciences 0302 clinical medicine Leukemia Myelogenous Chronic BCR-ABL Positive hemic and lymphatic diseases Internal medicine Nitriles Humans Medicine Philadelphia Chromosome education Protein Kinase Inhibitors neoplasms education.field_of_study Aniline Compounds Hematology business.industry Nuclear Proteins Myeloid leukemia Middle Aged Isocitrate Dehydrogenase Neoplasm Proteins Leukemia Myeloid Acute medicine.anatomical_structure 030220 oncology & carcinogenesis Mutation Quinolines Cancer research Bone marrow business Nucleophosmin Bosutinib 030215 immunology medicine.drug |
| Zdroj: | International Journal of Hematology. 113:936-940 |
| ISSN: | 1865-3774 0925-5710 |
| DOI: | 10.1007/s12185-020-03074-7 |
| Popis: | Tyrosine kinase inhibitors (TKIs) are standard therapies for chronic myeloid leukemia (CML) that can eradicate Ph-positive leukemic cells. However, disease control is not achievable in a minority of cases, most commonly due to evolution of TKI-resistant clones. There have also been rare cases of emergence of Ph-negative clones with other cytogenetic abnormalities, and, less commonly, development of Ph-negative acute myeloid leukemia (AML), whose molecular pathogenesis is largely unknown. Here we report molecular features of a patient with Ph + CML who developed Ph-negative AML after showing a major molecular response to dasatinib. A 55-year-old man was diagnosed with CML. He achieved a complete cytogenetic response three months after dasatinib therapy but developed AML with normal karyotype 1 year later. After receiving induction and consolidation chemotherapy for AML, the patient achieved complete remission with no evidence of CML under maintenance with bosutinib. Targeted sequencing of serial bone marrow samples identified mutations in IDH2 and NPM1 in the Ph-negative AML cells, which had not been detected in CML cells. These results suggest that Ph-negative AML in this patient originated from a preleukemic population, which might have expanded during or after the successful elimination of CML clones with TKI therapy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink