32 research outputs found
The evolution of cellular deficiency in GATA2 mutation.
To access publisher's full text version of this article click on the hyperlink at the bottom of the pageConstitutive heterozygous GATA2 mutation is associated with deafness, lymphedema, mononuclear cytopenias, infection, myelodysplasia (MDS), and acute myeloid leukemia. In this study, we describe a cross-sectional analysis of 24 patients and 6 relatives with 14 different frameshift or substitution mutations of GATA2. A pattern of dendritic cell, monocyte, B, and natural killer (NK) lymphoid deficiency (DCML deficiency) with elevated Fms-like tyrosine kinase 3 ligand (Flt3L) was observed in all 20 patients phenotyped, including patients with Emberger syndrome, monocytopenia with Mycobacterium avium complex (MonoMAC), and MDS. Four unaffected relatives had a normal phenotype indicating that cellular deficiency may evolve over time or is incompletely penetrant, while 2 developed subclinical cytopenias or elevated Flt3L. Patients with GATA2 mutation maintained higher hemoglobin, neutrophils, and platelets and were younger than controls with acquired MDS and wild-type GATA2. Frameshift mutations were associated with earlier age of clinical presentation than substitution mutations. Elevated Flt3L, loss of bone marrow progenitors, and clonal myelopoiesis were early signs of disease evolution. Clinical progression was associated with increasingly elevated Flt3L, depletion of transitional B cells, CD56(bright) NK cells, naĂŻve T cells, and accumulation of terminally differentiated NK and CD8(+) memory T cells. These studies provide a framework for clinical and laboratory monitoring of patients with GATA2 mutation and may inform therapeutic decision-making.Lymphoma and Leukaemia Research
British Society of Hematology
Bright Red
George Walker Trust
Wellcome Trus
Immunology for medical students. Third edition
Philadelphia, PAxii, 306 hlm.: bibl. ref., index; 28 c
Laboratory indicators for monitoring HIV disease
Immunological monitoring of disease progression following HIV infection
and seroconversion illness, latency and AIDS, not only helps in the
basic investigation of the natural history of the viral infection in
man, but also can assist in prognosis and treatment of AIDS-defining
illnesses. However, outside clinical trials, these tests should be
selected and used in clinical practice only if they are validated as
relevant and effective. The absolute CD4+ T-helper lymphocyte count,
measured by flow cytometry, has emerged as the best available
investigation, but needs care in sampling due to diurnal and circadian
rhythms, effects of age, pregnancy, therapy, intercurrent infections
and technique. Sampling should provide a baseline and trends - monthly
intervals initially, then quarterly in uncomplicated cases