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Genetic regulation of fetal haemoglobin in inherited bone marrow failure syndromes
Author(s) -
Alter Blanche P.,
Rosenberg Philip S.,
Day Thomas,
Menzel Stephan,
Giri Neelam,
Savage Sharon A.,
Thein Swee Lay
Publication year - 2013
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12399
Subject(s) - macrocytosis , erythropoiesis , fanconi anemia , bone marrow failure , erythropoietin , ineffective erythropoiesis , bone marrow , dyskeratosis congenita , medicine , allele , anemia , immunology , endocrinology , biology , genetics , haematopoiesis , stem cell , gene , dna repair , telomere
Summary Patients with inherited bone marrow failure syndromes ( IBMFS ) have ‘stress erythropoiesis’, with anaemia, macrocytosis, increased fetal haemoglobin (Hb F) and high erythropoietin levels. In haemoglobinopathies, Hb F levels are regulated by 3 quantitative trait loci, HBS 1L‐ MYB , BCL 11A and Xmn1 ‐ HBG 2 . In our study of 97 patients with an IBMFS , increased Hb F was associated with young age, male gender, anaemia, high erythropoietin levels, and alternative alleles in Xmn1 ‐ HBG 2 [adjusted P = 0·04 for the total group, driven by Fanconi anaemia ( P = 0·02) and dyskeratosis congenita ( P = 0·09)]. Thus Hb F is regulated in IBMFS by Xmn1 ‐ HBG 2, as it is in the haemoglobinopathies.