GATA2 deficiency-associated bone marrow disorder differs from idiopathic aplastic anemia - PubMed (original) (raw)

Comparative Study

. 2015 Jan 1;125(1):56-70.

doi: 10.1182/blood-2014-06-580340. Epub 2014 Oct 30.

Danielle M Townsley 2, Amy P Hsu 3, Diane C Arthur 1, Christa S Zerbe 3, Jennifer Cuellar-Rodriguez 3, Dennis D Hickstein 4, Sergio D Rosenzweig 5, Raul C Braylan 6, Neal S Young 2, Steven M Holland 3, Katherine R Calvo 6

Affiliations

Comparative Study

GATA2 deficiency-associated bone marrow disorder differs from idiopathic aplastic anemia

Karthik A Ganapathi et al. Blood. 2015.

Abstract

Germ-line GATA2 gene mutations, leading to haploinsufficiency, have been identified in patients with familial myelodysplastic syndrome/acute myeloid leukemia, monocytopenia and mycobacterial infections, Emberger syndrome, and dendritic cell, monocyte, B-, and NK-cell deficiency. GATA2 mutations have also been reported in a minority of patients with congenital neutropenia and aplastic anemia (AA). The bone marrow (BM) from patients with GATA2 deficiency is typically hypocellular, with varying degrees of dysplasia. Distinguishing GATA2 patients from those with AA is critical for selecting appropriate therapy. We compared the BM flow cytometric, morphologic, and cytogenetic features of 28 GATA2 patients with those of 32 patients being evaluated for idiopathic AA. The marrow of GATA2 patients had severely reduced monocytes, B cells, and NK cells; absent hematogones; and inverted CD4:CD8 ratios. Atypical megakaryocytes and abnormal cytogenetics were more common in GATA2 marrows. CD34(+) cells were comparably reduced in GATA2 and AA. Using these criteria, we prospectively identified 4 of 32 patients with suspected AA who had features suspicious for GATA2 mutations, later confirmed by DNA sequencing. Our results show that routine BM flow cytometry, morphology, and cytogenetics in patients who present with cytopenia(s) can identify patients for whom GATA2 sequencing is indicated.

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Figures

Figure 1

Figure 1

Peripheral blood indices of GATA2 and AA patients. (A) GATA2 and AA patients have comparable ages, hemoglobin levels, and WBC counts, but GATA2 patients have higher platelet, neutrophil count, and lower lymphocyte count compared with AA patients. (B) GATA2 patients have reduced peripheral blood monocytes, B cells, and NK cells, and relatively increased T cells compared with AA patients.

Figure 2

Figure 2

Bone marrow flow cytometric analysis of monocytes and lymphoid subsets in GATA2 and AA patients. (A) GATA2 patients have reduced bone marrow monocytes (CD33+, HLA-DR+), mature B cells (CD19+, CD20+), and NK cells (sCD3−, CD56+) compared with AA patients. (B) A subset of GATA2 patients has atypical CD19−CD56+ plasma cells (gating performed on CD38+, CD138+ positive population), which are not identified in AA patients.

Figure 3

Figure 3

Comparison of T-cell subsets between GATA2 and AA patients. (A) GATA2 patients have relatively increased bone marrow T cells, (B) inverted CD4:CD8 ratios, (C) increased CD3+CD56+, and (D) increased CD3+CD57+ T-cell subsets compared with AA patients.

Figure 4

Figure 4

Comparison of bone marrow precursor cells between GATA2 and AA patients. (A) GATA2 and AA patients have comparable levels of CD34-positive cells. (B) GATA2 patients have absent hematogones compared with AA patients.

Figure 5

Figure 5

Comparison of peripheral blood and bone marrow morphologic and immunohistochemical features between GATA2 and AA patients. GATA2 patient marrows have greater overall cellularity, increased megakaryocytes with atypical features (highlighted by CD61), but overall similar numbers of CD34-positive cells compared with AA marrows. A subset of GATA2 patients has hypogranular circulating neutrophils.

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