التفاصيل البيبلوغرافية
| العنوان: |
Therapy-related acute myeloid leukemia developing 14 years after allogeneic hematopoietic stem cell transplantation, from a persistent R882H-DNMT3A mutated clone of patient origin. |
| المؤلفون: |
Martín, Iván1 marcasi@alumni.uv.es, Navarro, Blanca1 nacublan@ext.uv.es, Villamón, Eva1 eva.villamon@uv.es, Solano, Carlos1,2 carlos.solano@uv.es, Serrano, Alicia1, Calabuig, Marisa1, Amat, Paula1, Domingo, Fernando1, Abellán, Rosario3 m.rosario.abellan@uv.es, García, Francisca1, Olivares, María Dolores3, Chaves, Francisco Javier3 felipe.chaves@uv.es, Tormo, Mar1 tormo_mar@gva.es, Hernández-Boluda, Juan Carlos1 hernandez_jca@gva.es |
| المصدر: |
Experimental & Molecular Pathology. Aug2018, Vol. 105 Issue 1, p139-143. 5p. |
| مصطلحات موضوعية: |
*ACUTE myeloid leukemia treatment, *HEMATOPOIETIC stem cell transplantation, *GENETIC mutation, *CELL-mediated cytotoxicity, *MOLECULAR cloning |
| مستخلص: |
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. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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