High Frequency of GATA2 Mutations in Patients with Mild Chronic Neutropenia Evolving to MonoMac Syndrome, Myelodysplasia, and Acute Myeloid Leukemia

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2012 Dec 11

PMID 23223431

Citations 109

Authors

Marlene Pasquet

Christine Bellanne-Chantelot

Suzanne Tavitian

Nais Prade

Blandine Beaupain

Olivier Larochelle

Arnaud Petit

Pierre Rohrlich

Christophe Ferrand

Eric Van den Neste

Helene A Poirel

Thierry Lamy

Marie Ouachee-Chardin

Veronique Mansat-De Mas

Jill Corre

Christian Recher

Genevieve Plat

Francoise Bachelerie

Jean Donadieu

Eric Delabesse

Affiliations

Soon will be listed here.

Abstract

Unlabelled: Congenital neutropenia is a group of genetic disorders that involve chronic neutropenia and susceptibility to infections. These neutropenias may be isolated or associated with immunologic defects or extra-hematopoietic manifestations. Complications may occur as infectious diseases, but also less frequently as myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Recently, the transcription factor GATA2 has been identified as a new predisposing gene for familial AML/MDS. In the present study, we describe the initial identification by exome sequencing of a GATA2 R396Q mutation in a family with a history of chronic mild neutropenia evolving to AML and/or MDS. The subsequent analysis of the French Severe Chronic Neutropenia Registry allowed the identification of 6 additional pedigrees and 10 patients with 6 different and not previously reportedGATA2 mutations (R204X, E224X, R330X, A372T, M388V, and a complete deletion of the GATA2 locus). The frequent evolution to MDS and AML in these patients reveals the importance of screening GATA2 in chronic neutropenia associated with monocytopenia because of the frequent hematopoietic transformation, variable clinical expression at onset, and the need for aggressive therapy in patients with poor clinical outcome.

Key Points: Mutations of key transcription factor in myeloid malignancies.

Citing Articles

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