RESUMEN
We evaluated clinical characteristics and outcome on imatinib of 22 patients with myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRB. Median age was 49 years (range 20-80), 91% were male. Fifteen different PDGFRB fusion genes were identified. Eosinophilia was absent in 4/19 (21%) cases and only 11/19 (58%) cases had eosinophils ≥1.5×109/L. On imatinib, 17/17 (100%) patients in chronic phase achieved complete hematologic remission after median 2 months (range 0-13)â. Complete cytogenetic remission and/or complete molecular remission by RT-PCR were achieved in 12/13 (92%) and 12/14 patients (86%) after median 10 (range 3-34) and 19 months (range 7-110), respectively. In patients with blast phase (myeloid, n = 2; lymphoid, n = 3), treatment included combinations of imatinib (n = 5), intensive chemotherapy (n = 3), and/or allogeneic stem cell transplantation (n = 3). All 3 transplanted patients (complex karyotype, n = 2) experienced early relapse. Initially, patients were treated with imatinib 400 mg/day (n = 15) or 100 mg/day (n = 7), the dose was reduced from 400 mg/day to 100 mg/day during follow-up in 9 patients. After a median treatment of 71 months (range 1-135), the 5-year survival rate was 83%; 4/22 (18%) patients died (chronic phase; n = 2; blast phase, n = 2) due to progression (n = 3) or comorbidity while in remission (n = 1). Of note, 3/4 patients had a complex karyotype. In summary, the most important characteristics of myeloid/lymphoid neoplasms with rearrangement of PDGFRB include (a) male predominance, (b) frequent lack of hypereosinophilia,
Asunto(s)
Crisis Blástica , Eosinofilia , Reordenamiento Génico , Neoplasias Hematológicas , Mesilato de Imatinib/administración & dosificación , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/genética , Cariotipo Anormal , Adulto , Anciano , Anciano de 80 o más Años , Crisis Blástica/tratamiento farmacológico , Crisis Blástica/genética , Crisis Blástica/mortalidad , Crisis Blástica/patología , Supervivencia sin Enfermedad , Eosinofilia/tratamiento farmacológico , Eosinofilia/genética , Eosinofilia/mortalidad , Eosinofilia/patología , Femenino , Estudios de Seguimiento , Neoplasias Hematológicas/tratamiento farmacológico , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/patología , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Riesgo , Factores Sexuales , Tasa de SupervivenciaRESUMEN
In eosinophilia-associated myeloproliferative neoplasms (MPN-eo), constitutive activation of protein tyrosine kinases (TK) as consequence of translocations, inversions, or insertions and creation of TK fusion genes is recurrently observed. The most commonly involved TK and their potential TK inhibitors include PDGFRA at 4q12 or PDGFRB at 5q33 (imatinib), FGFR1 at 8p11 (ponatinib), and JAK2 at 9p24 (ruxolitinib). We here report the identification of three new PDGFRB fusion genes in three male MPN-eo patients: MPRIP-PDGFRB in a case with t(5;17)(q33;p11), CPSF6-PDGFRB in a case with t(5;12)(q33;q15), and GOLGB1-PDGFRB in a case with t(3;5)(q13;q33). The fusion proteins identified by 5'-rapid amplification of cDNA ends polymerase chain reaction (PCR) or DNA-based long distance inverse PCR are predicted to contain the TK domain of PDGFRB. The partner genes contain domains like coiled-coil structures, which are likely to cause dimerization and activation of the TK. In all patients, imatinib induced rapid and durable complete remissions.