Acute promyelocytic leukemia in a long-standing HIV-positive patient: Case report and literature review.

The use of antiretroviral therapy has drastically improved the life quality and prognosis of people living with the human immunodeficiency virus (HIV). The risk of acute myeloid leukemia (AML) currently does not appear to be significantly increased compared to the general population. Acute promyelocytic leukemia (APL), infrequent in people with HIV, is a distinct subtype of AML with unique molecular pathogenesis, clinical manifestations, and treatment. Herein we describe a fatal case of APL hypogranular variant in an HIV-positive patient presenting with hyperleukocytosis. Also, we conducted a literature review of the ten cases reported so far.

Myeloid malignancies-related somatic mutations in aging individuals.

We search for the presence of somatic mutations in 12 genes related to MDS, MPN, and AML in a Brazilian cohort composed of 609 elderly individuals from a census-based sample.

Genetic Alterations in Essential Thrombocythemia Progression to Acute Myeloid Leukemia: A Case Series and Review of the Literature.

The genetic events associated with transformation of myeloproliferative neoplasms (MPNs) to secondary acute myeloid leukemia (sAML), particularly in the subgroup of essential thrombocythemia (ET) patients, remain incompletely understood. Deep studies using high-throughput methods might lead to a better understanding of genetic landscape of ET patients who transformed to sAML. We performed array-based comparative genomic hybridization (aCGH) and whole exome sequencing (WES) to analyze paired samples from ET and sAML phases. We investigated five patients with previous history of MPN, which four had initial diagnosis of ET (one case harboring JAK2 p.Val617Phe and the remaining three CALR type II p.Lys385fs*47), and one was diagnosed with MPN/myelodysplastic syndrome with thrombocytosis (SF3B1 p.Lys700Glu). All were homogeneously treated with hydroxyurea, but subsequently transformed to sAML (mean time of 6 years/median of 4 years to transformation). Two of them have chromosomal abnormalities, and both acquire 2p gain and 5q deletion at sAML stage. The molecular mechanisms associated with leukemic progression in MPN patients are not clear. Our WES data showed TP53 alterations recurrently observed as mutations (missense and frameshift) and monoallelic loss. On the other hand, aCGH showed novel chromosome abnormalities (+2p and del5q) potentially associated with disease progression. The results reported here add valuable information to the still fragmented molecular basis of ET to sAML evolution. Further studies are necessary to identify minimal deleted/amplified region and genes relevant to sAML transformation.

TET2 expression level and 5-hydroxymethylcytosine are decreased in refractory cytopenia of childhood.

Myelodysplastic syndromes (MDS) are myeloid malignancies characterized by ineffective hematopoiesis, dysplasia, peripheral cytopenia and increased risk of progression to acute myeloid leukemia. Refractory cytopenia of childhood (RCC) is the most common subtype of pediatric MDS and has overlapping clinical features with viral infections and autoimmune disorders. Mutations in TET2 gene are found in about 20-25% of adult MDS and are associated with a decrease in 5-hydroxymethylcytosine (5-hmC) content. TET2 deregulation and its malignant potential were reported in adult but not in pediatric MDS. We evaluated the gene expression and the presence of mutations in TET2 gene in 19 patients with RCC. TET2 expression level was correlated with 5-hmC amount in DNA and possible regulatory epigenetic mechanisms. One out of 19 pediatric patients with RCC was a carrier of a TET2 mutation. TET2 expression and 5-hmC levels were decreased in patients when compared to a disease-free group. Lower expression was not associated to the presence of mutation or with the status of promoter methylation, but a significant correlation with microRNA-22 expression was found. These findings suggested that TET2 downregulation and low levels of 5-hmC are inversely related to miR-22 expression. The existence of a regulatory loop between microRNA-22 and TET2 may play a role in MDS pathogenesis.

A mutação JAK2 V617F e as síndromes mieloproliferativas / JAK2 V617F mutation and the myeloproliferative disorders

Síndromes mieloproliferativas (SMPs) são doenças hematopoéticas de origem clonal que apresentam amplificação de uma ou mais linhagens mielóides. Policitemia vera (PV), trombocitemia essencial (TE), mielofibrose idiopática (MF) e leucemia mielóide crônica (LMC) são consideradas SMPs clássicas e apresentam características clínicas e biológicas comuns. Ao contrário de LMC, cuja etiologia está relacionada à proteína constitutivamente ativa Bcr-Abl, o mecanismo molecular de PV, TE e MF permaneceu por muito tempo desconhecido. Esta revisão se foca na recente descoberta da mutação JAK2 V617F em pacientes com PV, TE e MF, sua relação com o fenótipo mieloproliferativo e implicações na abordagem clínica de pacientes.

Myeloproliferative disorders are clonal hematopoietic diseases that are characterized by the amplification of one or more myeloid lineages. Polycythemia vera, essential thrombocythemia, idiopathic myelofibrosis and chronic myeloid leukemia are considered classic myeloproliferative disorders and share common clinical and biological features. While the genetic basis of chronic myeloid leukemia is shown to be the constitutive active protein BCR-ABL, the main molecular lesions in polycythemia vera, essential thrombocythemia and idiopathic myelofibrosis remain unknown. This review focuses on the recent discovery of the JAK2 V617F mutation, its relationship to the myeloproliferative phenotype and implications in the clinical approach of patients.