Global down-regulation of HOX gene expression in PML-RARα+ acute promyelocytic leukemia identified by small-array real-time PCR
2003; Elsevier BV; Volume: 101; Issue: 4 Linguagem: Inglês
10.1182/blood.v101.4.1558
ISSN1528-0020
AutoresAlexander Thompson, Michael F. Quinn, David Grimwade, C.M. O'Neill, Momin Ahmed, Sean Grimes, Mary Frances McMullin, Finbarr E. Cotter, Terence R.J. Lappin,
Tópico(s)Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
ResumoAcute promyelocytic leukemia (APL) is associated with a reciprocal and balanced translocation involving the retinoic acid receptor-α(RARα). All-trans retinoic acid (ATRA) is used to treat APL and is a potent morphogen that regulatesHOX gene expression in embryogenesis and organogenesis.HOX genes are also involved in hematopoiesis and leukemogenesis. Thirty-nine mammalian HOX genes have been identified and classified into 13 paralogous groups clustered on 4 chromosomes. They encode a complex network of transcription regulatory proteins whose precise targets remain poorly understood. The overall function of the network appears to be dictated by gene dosage. To investigate the mechanisms involved in HOX gene regulation in hematopoiesis and leukemogenesis by precise measurement of individual HOX genes, a small-array real-timeHOX (SMART-HOX) quantitative polymerase chain reaction (PCR) platform was designed and validated. Application of SMART-HOX to 16 APL bone marrow samples revealed a global down-regulation of 26 HOX genes compared with normal controls. HOX gene expression was also altered during differentiation induced by ATRA in thePML-RARα+ NB4 cell line. PML-RARα fusion proteins have been reported to act as part of a repressor complex during myeloid cell differentiation, and a model linkingHOX gene expression to this PML-RARα repressor complex is now proposed.
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