Hematology/oncology clinics of North America
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Hematol. Oncol. Clin. North Am. · Aug 2018
ReviewIntroduction to Acquired and Inherited Bone Marrow Failure.
Acquired aplastic anemia and inherited bone marrow failure syndromes both present with pancytopenia and must be distinguished because they have differences in treatment decisions and continued monitoring requirements. Advances in the genetic interrogation of patient samples have led to identification of inherited germline diseases and appreciation that patients with inherited bone marrow failure disorders may be normal in appearance with few expected clinical clues. Somatic mutations in aplastic anemia may have prognostic value. Hematopoietic stem cells from inherited marrow failure diseases can correct the proliferative defect and may develop further somatic mutations that progress to myelodysplastic syndrome or acute myeloid leukemia.
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GATA2 deficiency is an immunodeficiency and bone marrow failure disorder caused by pathogenic variants in GATA2. It is inherited in an autosomal-dominant pattern or can be due to de novo sporadic germline mutation. ⋯ Patients may suffer from disseminated human papilloma virus and mycobacterial infections, pulmonary alveolar proteinosis, and lymphedema. The bone marrow eventually takes on a characteristic hypocellular myelodysplasia with loss of monocytes and hematogones, megakaryocytes with separated nuclear lobes, micromegakaryocytes, and megakaryocytes with hypolobated nuclei.
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Hematol. Oncol. Clin. North Am. · Aug 2018
ReviewSignificance of Clonal Mutations in Bone Marrow Failure and Inherited Myelodysplastic Syndrome/Acute Myeloid Leukemia Predisposition Syndromes.
Clonal hematopoiesis as a hallmark of myelodysplastic syndrome (MDS) is mediated by the selective advantage of clonal hematopoietic stem cells in a context-specific manner. Although primary MDS emerges without known predisposing cause and is associated with advanced age, secondary MDS may develop in younger patients with bone marrow failure syndromes or after exposure to chemotherapy, respectively. This article discusses recent advances in the understanding of context-dependent clonal hematopoiesis in MDS with focus on clonal evolution in inherited and acquired bone marrow failure syndromes.
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Hematol. Oncol. Clin. North Am. · Aug 2018
ReviewEvaluation and Management of Hematopoietic Failure in Dyskeratosis Congenita.
Dyskeratosis congenita (DC) is a rare, inherited bone marrow failure (BMF) syndrome characterized by variable manifestations and ages of onset, and predisposition to cancer. DC is one of a spectrum of diseases caused by mutations in genes regulating telomere maintenance, collectively referred to as telomere biology disorders (TBDs). ⋯ Timely diagnosis of underlying TBD in patients with BMF affects treatment and has been facilitated by increased awareness and availability of diagnostic tests in recent years. This article summarizes the pathophysiology, evaluation, and management of hematopoietic failure in patients with DC and other TBDs.