Identification of a transforming MYB-GATA1 fusion gene in acute basophilic leukemia: a new entity in male infants

• Published in: Blood 2011-05, Vol.117 (21), p.5719-5722
• Main Authors: Quelen, Cathy, Lippert, Eric, Struski, Stephanie, Demur, Cécile, Soler, Gwendoline, Prade, Nais, Delabesse, Eric, Broccardo, Cyril, Dastugue, Nicole, Mahon, François-Xavier, Brousset, Pierre
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Blotting, Western; Cancer; Chromosomes, Human, Pair 6; Chromosomes, Human, Pair 6 - genetics; Chromosomes, Human, X; Chromosomes, Human, X - genetics; Female; GATA1 Transcription Factor; GATA1 Transcription Factor - genetics; Hematologic and hematopoietic diseases; Humans; In Situ Hybridization, Fluorescence; Infant; Karyotyping; Leukemia, Basophilic, Acute; Leukemia, Basophilic, Acute - genetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Life Sciences; Male; Medical sciences; Mice; Mice, Inbred C57BL; Oncogene Proteins, Fusion; Oncogene Proteins, Fusion - genetics; Oncogenes; Oncogenes - genetics; Prognosis; Proto-Oncogene Proteins c-myb; Proto-Oncogene Proteins c-myb - genetics; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Messenger - genetics; Translocation, Genetic; Tumor Stem Cell Assay
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2011-01-333013

Acute basophilic leukemia (ABL) is a rare subtype of acute leukemia with clinical features and symptoms related to hyperhistaminemia because of excessive growth of basophils. No known recurrent cytogenetic abnormality is associated with this leukemia. Rare cases of t(X;6)(p11;q23) translocation have been described but these were sporadic. We report here 4 cases of ABL with a t(X;6)(p11;q23) translocation occurring in male infants. Because of its location on chromosome 6q23, MYB was a good candidate gene. Our molecular investigations, based on fluorescence in situ hybridization and rapid amplification of cDNA ends, revealed that the translocation generated a MYB-GATA1 fusion gene. Expression of MYB-GATA1 in mouse lineage-negative cells committed them to the granulocyte lineage and blocked at an early stage of differentiation. Taken together, these results establish, for the first time, a link between a recurrent chromosomal translocation and the development of this particular subtype of infant leukemia.