Common Genetic Variants of Fetal Hemoglobin Modify Hematological Phenotypes in MDS/MPN/Myeloma Patients Receiving Cytotoxic Drugs

Genetic studies identify common variants within the HBS1L-MYB intergenic region (HMIP), BCL11A, and Xmn1-HBG2 as associated with elevated fetal hemoglobin (HbF) levels other clinically important human hematological traits. Recent suggest HbF is a predictor of outcome in MDS/AML patients receiving decitabine. We assessed effects genetic on traits Myeloproliferative Neoplasm (MPN), Myelodysplastic Syndrome (MDS) myeloma HbF-inducing therapy to determine potential for predicting treatment response. Seven at HMIP, Xmn1-HGB2 loci were genotyped 89 MPN Hydroxyurea (HU), Lenalidomide, MDS Azacytidine. association was seen rs9494142 (HMIP) HU (p = 0.04) rs1427407 (BCL11A) Lenalidomide 0.002). HMIP rs6920211 influenced baseline platelets response 0.02). significantly increased negating thrombocytopenic tendency Lenalidomide. These showed discordant minor allele frequencies MDS/MPN/myeloma compared wider European population data. This small study finding together implication these disease biology warranting larger prospective genotype-phenotype studies.