RESUMO
Acute megakaryoblastic leukemia (M7 AML) is a rare subtype of acute myeloid leukemia in adults, the incidence of which is higher in children aged 1 to 3 years, especially in patients with Down Syndrome; and in the age group between 60 and 70 years old, with an adverse prognosis. We report the case of a 28-year-old male patient, with a history of non-seminoma germ cell tumour of the testis, diagnosed with M7 AML. Nine months after performing an orchiectomy to remove the testicular tumour, the patient developed dyspnea, dry cough and asthenia, associated with the presence of erythematous-purple lesions on the skin, ascites and pleural effusion. The myelogram demonstrated medullary hypocellularity, with the presence of 53% of blastic, pleomorphic and bulky cells, with positivity for the markers CD34, CD31 and CD117 in immature cells in immunohistochemistry. Despite undergoing cycles of chemotherapy with cisplatin and a BEP regimen (Bleomycin, Etoposide and Cisplatin), the patient presented with chest tomography with the presence of pulmonary nodules and magnetic resonance imaging of the skull and neuraxial with infiltration of the bone marrow in the spine and cranial vault, resulting in with neurological impairment and died. In view of the case presented, we observed agreement with previous reports of the adverse prognosis of M7 AML in young adults and we questioned its relationship with germ cell tumour. (AU)
A leucemia megacarioblástica aguda (LMA M7) é um subtipo raro em adultos de leucemia mielóide aguda, cuja incidência é maior em crianças de 1 a 3 anos, especialmente em pacientes portadores de Síndrome de Down; e na faixa etária entre 60 e 70 anos, com um prognóstico adverso. Relatamos o caso de um paciente, do sexo masculino, 28 anos, com histórico de tumor germinativo não seminoma de testículo, diagnosticado com LMA M7. Nove meses após a realização de uma orquiectomia para a retirada do tumor testicular, o paciente apresentou quadro de dispneia, tosse seca e astenia, associado a presença de lesões eritemato-arroxeadas na pele, ascite e derrame pleural. O mielograma demonstrou hipocelularidade medular, com presença de 53% de células blásticas, pleomórficas e volumosas, com a positividade para os marcadores CD34, CD31 e CD117 em células imaturas na imunohistoquímica. Apesar da realização de ciclos de quimioterapia com cisplatina e esquema BEP (Bleomicina, Etoposídeo e Cisplatina), o paciente apresentou Tomografia de tórax com presença de nódulos pulmonares e ressonância magnética de crânio e neuroeixo com infiltração da medula óssea em coluna vertebral e calota craniana, intercorrendo com comprometimento neurológico e foi a óbito. Diante do caso apresentado observamos a concordância com relatos prévios do prognóstico adverso da LMA M7 em jovens adultos e indagamos a sua relação com o tumor de células germinativas. (AU)
RESUMO
Los pacientes con síndrome de Down tienen un riesgo más elevado de presentar leucemia megacarioblástica aguda (LMCA). Un 10% de los recién nacidos con ese síndrome presentan un cuadro de mielopoyesis anormal transitoria (MAT), indistinguible de la LMCA, que en general remite espontáneamente. En ambos grupos de pacientes se describió una alta incidencia de mutaciones en el gen GATA-1. Se analizaron 14 muestras de ADN de médula ósea (10 MAT/4 LMCA) correspondientes a 13 pacientes con Síndrome de Down mediante PCR y secuenciación, para describir la frecuencia y las características de las mutaciones en el gen GATA-1 en la población estudiada y sus consecuencias a nivel proteico. Se detectaron mutaciones en 10 de 10 MAT y en 3 de 4 LMCA, que a nivel proteico originarían un codón de terminación prematuro (n= 5), alteraciones en el sitio de corte y empalme (splicing) (n= 6) o cambio de secuencia (n= 3). Se confrmó la alta frecuencia de mutaciones en el gen GATA-1 en recién nacidos con Síndrome de Down y MAT o LMCA.
Patients with Down's Syndrome have a higher risk of developing acute megakaryoblastic leukemia (AML). Ten per cent of newborn infants with this syndrome have transient abnormal myelopoiesis (TAM), indistinguishable from AML, which generally remits spontaneously. A high incidence of GATA-1 gene mutations was described in both groups of patients. Fourteen bone marrow DNA samples (10 ATM/4 AML) were analyzed by PCR and sequencing; these samples were obtained from 13 patients with Down's Syndrome to describe the rate and mutation characteristics of the GATA-1 gene in the studied population and its consequences at a protein level. Mutations were detected in 10 out of 10 TAM and in 3 out of 4 AML, which at a protein level would result in an early termination codon (n= 5), alterations in the splicing site (n= 6) or sequence change (n= 3). The high rate of GATA-1 gene mutations was confirmed in newborn infants with Down's Syndrome and MAT or AML.