RESUMO
OBJECTIVES: Hypocellular acute myeloid leukemia (AML) is uncommon. Despite the prognostic and therapeutic importance of mutational analysis, the mutational landscape of hypocellular AML is not well understood. METHODS: We identified 25 patients with hypocellular AML, and 141 patients with nonhypocellular AML were identified as a control group. We applied next-generation sequencing for the first time to profile this entity. RESULTS: The hypocellular AML patients were older than those with nonhypocellular AML (P = .037). At diagnosis, hypocellular AML had lower leukocyte counts (P = .012), higher hemoglobin (P = .003), and lower blast counts in the peripheral blood (P < .001) and bone marrow (P = .003). Hypocellular AML was less likely to have mutations involving cell proliferation (P = .027) and NPM1 (P = .022) compared with nonhypocellular AML. Hypocellular AML showed a high incidence of spliceosomal mutations and myelodysplastic syndrome-defining chromosome abnormalities (65%), but the incidence was not significantly different from that in nonhypocellular AML. There was no significant survival difference between hypocellular and nonhypocellular AML. CONCLUSIONS: To our knowledge, this study is the first to demonstrate hypocellular AML showed fewer genetic alterations involving cell proliferation and NPM1 when compared directly with nonhypocellular AML; this finding likely contributes to the low marrow cellularity in at least a portion of the patients with hypocellular AML.
Assuntos
Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Proteínas Nucleares/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Proliferação de Células/genética , Análise Mutacional de DNA , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Nucleofosmina , Adulto JovemRESUMO
About 10% of women of reproductive age are unable to conceive or carry a pregnancy to term. Female factors alone account for at least 35% of all infertility cases and comprise a wide range of causes affecting ovarian development, maturation of oocytes, and fertilization competence, as well as the potential of a fertilized egg for preimplantation development, implantation, and fetal growth. Genetic abnormalities leading to infertility in females comprise large chromosome abnormalities, submicroscopic chromosome deletion and duplications, and DNA sequence variations in the genes that control numerous biological processes implicated in oogenesis, maintenance of ovarian reserve, hormonal signaling, and anatomical and functional development of female reproductive organs. Despite the great number of genes implicated in reproductive physiology by the study of animal models, only a subset of these genes is associated with human infertility. In this review, we mainly focus on genetic alterations identified in humans and summarize recent knowledge on the molecular pathways of oocyte development and maturation, the crucial role of maternal-effect factors during embryogenesis, and genetic conditions associated with ovarian dysgenesis, primary ovarian insufficiency, early embryonic lethality, and infertility.
Assuntos
Infertilidade Feminina/genética , Oogênese/genética , Animais , Modelos Animais de Doenças , Desenvolvimento Embrionário/genética , Feminino , Humanos , Relações Materno-Fetais/fisiologia , Reserva Ovariana/genética , Gravidez , Insuficiência Ovariana Primária/diagnóstico , Insuficiência Ovariana Primária/genética , Reprodução/genética , Transdução de Sinais/genéticaRESUMO
Genetic tools such as microarray and next-generation sequencing have initiated a new era for the diagnosis and management of patients with disorders of sex development (DSDs). These tools supplement the traditional approach to the evaluation and care of infants, children, and adolescents with DSDs. These tests can detect genetic variations known to be associated with DSDs, discover novel genetic variants, and elucidate novel mechanisms of gene regulation. Herein, we discuss these tests and their role in the management of patients with DSDs.