Loss of B cells and their precursors is the most constant feature of GATA-2 deficiency in childhood myelodysplastic syndrome - PubMed (original) (raw)
. 2016 Jun;101(6):707-16.
doi: 10.3324/haematol.2015.137711. Epub 2016 Mar 24.
Markéta Žaliová 1, Martina Suková 2, Marcin Wlodarski 3, Aleš Janda 3, Eva Froňková 4, Vít Campr 5, Kateřina Lejhancová 6, Ondřej Zapletal 7, Dagmar Pospíšilová 8, Zdeňka Černá 9, Tomáš Kuhn 10, Peter Švec 11, Vendula Pelková 1, Zuzana Zemanová 12, Gitte Kerndrup 13, Marry van den Heuvel-Eibrink 14, Vincent van der Velden 15, Charlotte Niemeyer 3, Tomáš Kalina 1, Jan Trka 4, Jan Starý 2, Ondřej Hrušák 4, Ester Mejstříková 16
Affiliations
- PMID: 27013649
- PMCID: PMC5013954
- DOI: 10.3324/haematol.2015.137711
Loss of B cells and their precursors is the most constant feature of GATA-2 deficiency in childhood myelodysplastic syndrome
Michaela Nováková et al. Haematologica. 2016 Jun.
Abstract
GATA-2 deficiency was recently described as common cause of overlapping syndromes of immunodeficiency, lymphedema, familiar myelodysplastic syndrome or acute myeloid leukemia. The aim of our study was to analyze bone marrow and peripheral blood samples of children with myelodysplastic syndrome or aplastic anemia to define prevalence of the GATA2 mutation and to assess whether mutations in GATA-2 transcription factor exhibit specific immunophenotypic features. The prevalence of a GATA2 mutation in a consecutively diagnosed cohort of children was 14% in advanced forms of myelodysplastic syndrome (refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and myelodysplasia-related acute myeloid leukemia), 17% in refractory cytopenia of childhood, and 0% in aplastic anemia. In GATA-2-deficient cases, we found the most profound B-cell lymphopenia, including its progenitors in blood and bone marrow, which correlated with significantly diminished intronRSS-Kde recombination excision circles in comparison to other myelodysplastic syndrome/aplastic anemia cases. The other typical features of GATA-2 deficiency (monocytopenia and natural killer cell lymphopenia) were less discriminative. In conclusion, we suggest screening for GATA2 mutations in pediatric myelodysplastic syndrome, preferentially in patients with impaired B-cell homeostasis in bone marrow and peripheral blood (low number of progenitors, intronRSS-Kde recombination excision circles and naïve cells).
Copyright© Ferrata Storti Foundation.
Figures
Figure 1.
Cell populations in bone marrow (BM). (A) B-cell subpopulations and kappa-deleting recombination excision circles (KRECs). (B) T-cell subpopulations and T-cell receptor excision circles (TRECs). (C) Natural killer cells. (D) Monocytes. (E) Progenitors. Braces indicate significant difference between the parameters using the non-parametric Mann-Whitney test (P<0.05). Black lines represent medians. A gray area indicates the range of control samples.
Figure 2.
Cell populations in peripheral blood (PB). (A) B cells and kappa-deleting recombination excision circles (KRECs). (B) T cells and T-cell receptor excision circles (TRECs). (C) Natural killer cells. (D) Monocytes. Braces indicate significant differences between parameters using the non-parametric Mann-Whitney test (P<0.05). A gray area indicates the range of control samples. Absolute counts are shown. In relative counts, similar results were found except for relative T cells, which were increased in GATA-2-deficient patients compared to controls.
Figure 3.
Follow-up peripheral blood (PB) samples of GATA-2-deficient patients. Each column represents one patient. Black lines represent medians. A gray area indicates a normal range for the age category of most of the patients [either 12–18 years for B cells, natural killer (NK) cells; >15 years for monocytes and neutrophils; or >16 years for class switched memory B cells and naïve B cells]. (A) B cells and B-cell subpopulations. (B) Monocytes, NK cells, neutrophils.
Figure 4.
Receiver operating characteristic curves for peripheral blood monocytes, B cells and natural killer (NK) cells in GATA-2-deficient patients in comparison with all other patients with aplastic anemia and myelodysplastic syndromes. Light green: relative B-cell count; dark green: absolute B-cell count; light red: relative monocyte count; dark red: absolute monocyte count; light blue: relative NK-cell count; dark blue: absolute NK-cell count.
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