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Blood, 1 August 2006, Vol. 108, No. 3, pp. 1077-1083.
Prepublished online as a Blood First Edition Paper on April 13, 2006; DOI 10.1182/blood-2006-01-008912.
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Submitted January 27, 2006
Accepted March 17, 2006
cMYB is involved in the regulation of fetal hemoglobin
production in adults
Jie Jiang, Steve Best, Stephan Menzel, Nicholas Silver, Mei I Lai, Gabriela L Surdulescu, Tim D Spector, and Swee Lay Thein*
Molecular Haematology, King's College London School of Medicine at King's College Hospital
Twin Research & Epidemiology Unit, King's College London School of Medicine at St Thomas' Hospital
* Corresponding author; email: sl.thein{at}kcl.ac.uk.
A quantitative trait locus (QTL) controlling HbF levels
has previously been mapped to chromosome 6q23 in an
Asian-Indian kindred with  thalassemia and
heterocellular hereditary persistence of fetal
hemoglobin (HPFH). Five protein-coding genes, ALDH8A1,
HBS1L, cMYB, AHI1 and PDE7B reside in this 1.5Mb
candidate interval of 6q23. To direct sequencing efforts
we compared the expression profiles of these five genes
between 12 individuals with elevated and 14 individuals
with normal HbF levels during adult erythropoiesis by
real time quantitative RT-PCR. Two genes, cMYB and
HBS1L, demonstrated simultaneous transcriptional down-
regulation in individuals with elevated HbF levels.
Transfection of K562 cells encoding human cDNA of cMYB
and HBS1L genes showed that while over-expression of
ectopic cMYB inhibited  -globin gene expression,
overexpression of HBS1L had no effect. Low levels of
cMYB were associated with low cell expansions,
accelerated erythroid maturation and higher number of
macrophages in erythroid cell culture. These
observations suggest that differences in the intrinsic
levels of cMYB may account for some of the variation in
adult HbF levels. The possible mechanism of cMYB
influencing to globin switching is
discussed.
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