Therapy-related acute myeloid leukemia developing 14 years after allogeneic hematopoietic stem cell transplantation, from a persistent R882H- DNMT3A mutated clone of patient origin
| Autor: | Iván Martín, Blanca Navarro, Francisco Javier Chaves, Francisca García, María Dolores Olivares, Marisa Calabuig, Rosario Abellán, Juan Carlos Hernández-Boluda, Alicia Serrano, Mar Tormo, Paula Amat, Carlos Solano, Eva Villamón, Fernando Domingo |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Male Oncology medicine.medical_specialty NPM1 Allogeneic transplantation medicine.medical_treatment Clinical Biochemistry Mutation Missense Clone (cell biology) Therapy-Related Acute Myeloid Leukemia Hematopoietic stem cell transplantation DNA Methyltransferase 3A Pathology and Forensic Medicine 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Humans Transplantation Homologous DNA (Cytosine-5-)-Methyltransferases Molecular Biology Bone Marrow Transplantation business.industry Myeloid leukemia Induction chemotherapy Transplantation Leukemia Myeloid Acute 030220 oncology & carcinogenesis business Nucleophosmin 030215 immunology |
| Zdroj: | Experimental and Molecular Pathology. 105:139-143 |
| ISSN: | 0014-4800 |
| Popis: | Background Therapy-related acute myeloid leukemia (t-AML) develops in patients with prior exposure to cytotoxic therapies. Selection of a pre-existing TP53 mutated clone prone to acquire additional mutational events has been suggested as the main pathogenic mechanism of t-AML. Here, we report a unique case of t-AML which developed from a pre-existing DNMT3A mutated clone that persisted in the patient for more than 10 years despite treatment with intensive chemotherapy and allogeneic hematopoietic stem cell transplantation (alloHSCT). Case presentation A 42-year-old male was diagnosed with AML harboring a normal karyotype and mutations in the NPM1 (c.863_864ins, p.W288 fs*12), DNMT3A (c.2645G > A, p.R882H), and IDH1 (c.395G > A, p.R132H) genes. He achieved complete remission with intensive chemotherapy and was subsequently submitted to alloHSCT. Eleven years later, he was given chemotherapy and radiotherapy to treat a lung carcinoma. Three years later, t-AML was diagnosed; the disease had arisen from a pre-existing DNMT3A mutated patient-origin clone that had subsequently acquired a TP53 mutation and a complex karyotype. Although a second transplantation was intended, the disease was refractory to induction chemotherapy, and the patient eventually died from disease complications. We retrospectively demonstrated the persistence and post-transplantation latency of the R882H- DNMT3A mutation using a real-time PCR allele-specific analysis at different time-points during the observation period. Discussion and conclusion The present case highlights the potential clinical implications of a R882H- DNMT3A mutated clone that persisted after conventional AML treatment, including alloHSCT. It also reinforces the notion of the importance of cell non-intrinsic factors, such as the hematopoietic-stress induced by chemotherapy and radiotherapy, as drivers of clonal expansion. |
| Databáze: | OpenAIRE |
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