Assuntos
Hemoglobinas , Transtornos Mieloproliferativos , Trombose Venosa , Humanos , Transtornos Mieloproliferativos/sangue , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/complicações , Trombose Venosa/sangue , Trombose Venosa/diagnóstico , Trombose Venosa/etiologia , Feminino , Masculino , Hemoglobinas/análise , Hemoglobinas/metabolismo , Pessoa de Meia-Idade , França/epidemiologia , Idoso , Adulto , Circulação Esplâncnica , Eritrócitos/metabolismo , Eritrócitos/patologia , Índices de EritrócitosRESUMO
INTRODUCTION: In BCR-ABL1-negative myeloproliferative neoplasms, myelofibrosis (MF) is either primary (PMF) or secondary (SMF) to polycythemia vera or essential thrombocythemia. MF is characterized by an increased risk of transformation to acute myeloid leukemia (AML) and a shortened life expectancy. METHODS: Because natural histories of PMF and SMF are different, we studied by targeted next generation sequencing the differences in the molecular landscape of 86 PMF and 59 SMF and compared their prognosis impact. RESULTS: PMF had more ASXL1 (47.7%) and SRSF2 (14%) gene mutations than SMF (respectively 27.1% and 3.4%, P = .04). Poorer survival was associated with RNA splicing mutations (especially SRSF2) and TP53 in PMF (P = .0003), and with ASXL1 and TP53 mutations in SMF (P < .0001). These mutations of poor prognosis were associated with biological features of scoring systems (DIPSS and MYSEC-PM score). Mutations in TP53/SRSF2 in PMF or TP53/ASXL1 in SMF were more frequent as the risk of these scores increased. This allowed for a better stratification of MF patients, especially within the DIPSS intermediate-1 risk group (DIPSS) or the MYSEC-PM high risk group. AML transformation occurred faster in SMF than in PMF and patients who transformed to AML were more SRSF2-mutated and less CALR-mutated at MF sampling. CONCLUSIONS: PMF and SMF have different but not specific molecular profiles and different prognosis depending on the molecular profile. This may be due to differences in disease history. Combining mutations and existing scores should improve prognosis assessment.
Assuntos
Calreticulina/genética , Janus Quinase 2/genética , Mutação , Receptores de Trombopoetina/genética , Trombocitemia Essencial , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Taxa de Sobrevida , Trombocitemia Essencial/genética , Trombocitemia Essencial/mortalidade , Trombocitemia Essencial/patologia , Trombocitemia Essencial/terapiaRESUMO
Donor cell leukemia (DCL) is an infrequent complication after allogeneic hematopoietic stem cell transplantation (HSCT). Its true incidence is difficult to assess, although improvements in chimerism studies contributed to a better diagnosis of DCL. We report two rare cases of donor cell-derived acute promyelocytic leukemia (APL). To our knowledge, only two cases have been described in the literature. Here, we report one male and one female patients with acute myeloid leukemia (AML), who developed an APL in donor cells after HSCT. The latency between HSCT and DCL was 279 and 43 months, respectively. Fluorescent in situ hybridation and chimerism monitoring analysis proved the donor origin of APL. Surprisingly, donor lymphocyte infusion provided a hematological response during 19 months in the female patient. The mechanisms associated with pathogenesis of DCL are unclear and seem to be multifactorial. Increasing worldwide allogeneic hematopoietic stem cell transplantation activity and potentially the age of donor could explain the increasing incidence of DCL in the future. It is highlighted that long-term follow up of recipients will allow to report all cases of DCL, to clarify the genetic landscape and factors which contribute to DCL, to understand the response to DLI.