ABSTRACT
BACKGROUND: GATA2 deficiency presents with a spectrum of phenotypes including increased susceptibility to viral and bacterial infections, multi-lineage cytopenias, aplastic anemia, leukemic transformation and lymphedema. Allogeneic transplantation is only curative therapy for GATA2 deficiency, but is associated with significant treatment related morbidity and mortality. Given the spectrum of clinical presentation, accurate diagnosis of GATA2 deficiency is necessary to identify patients early in their disease course when allogeneic bone marrow transplantation may be of clinical benefit. CASE PRESENTATION: In this report, we present a GATA2 mutation diagnosed in 23-year-old woman presenting with pancytopenia, recurring oral blisters, fatigue and chronic pain. We describe markedly low levels of mature B-cells in the blood and bone marrow and the absence of detectable blood dendritic cells with normal serum immunoglobulin levels and normal numbers of marrow plasma cells. She was ultimately diagnosed with GATA2 haplo-insufficiency due to a GATA2 germ-line mutation and underwent a successful allogeneic bone marrow transplant from a 10/10 HLA matched unrelated donor. CONCLUSIONS: The case illustrates the diagnostic difficulties in identifying GATA2 deficiencies and the importance of family history and genetic testing. GATA2 plays an important role in B-cell and dendritic cell development, and decreased numbers of those cells is a characteristic feature that should prompt consideration of GATA2 deficiency in a patient with pancytopenia. Maturation of B-cells to long-lived plasma cells is relatively unaffected in GATA2 deficiency. Allogeneic stem cell transplantation can correct immune-deficiencies and prevent leukemic transformation in patients with GATA2 deficiency.
ABSTRACT
Marginal zone lymphoma (MZL) is an uncommon indolent lymphoma classified into subtypes based on primary site of involvement: splenic, nodal and extranodal. MZLs' relative rarity has largely precluded adoption of a standard management strategy. Here, we provide an overview of the epidemiology, clinical behavior and therapeutic approaches for each subtype. Biologic insights into lymphomagenesis have identified B-cell receptor signaling as a rational therapeutic target. Recent clinical data suggest that novel agents targeting this pathway, including the Bruton's tyrosine kinase inhibitor, ibrutinib, show significant promise in treatment of relapsed MZL. More work is needed to evaluate these agents' activity in the front-line setting, possible combination regimens and the impact of resistance to B-cell receptor-targeted agents in order to optimize therapy in MZL.
