Pomalidomide augments fetal hemoglobin production without the myelosuppressive effects of hydroxyurea in transgenic sickle cell mice

Steffen E Meiler, Marlene Wade, Ferdane Kutlar, Shobha D. Yerigenahally, Yongjun Xue, Laure A. Moutouh-de Parseval, Laura G. Corral, Paul S. Swerdlow, Abdullah Kutlar

Research output: Contribution to journalArticle

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Abstract

Pharmacologic induction of fetal hemoglobin (HbF) expression is an effective treatment strategy for sickle cell disease (SCD) and β-thalassemia. Pomalidomide is a potent structural analog of thalidomide and member of a new class of immunomodulatory drugs. Recent reports demonstrated that pomalidomide reduced or eliminated transfusion requirements in certain hematologic malignancies and induced HbF ex vivo in CD34+progenitor cells from healthy and SCD donors. We investigated the effects of pomalidomide on erythropoiesis and hemoglobin synthesis in a transgenic mouse model of SCD. We found that 8 weeks of treatment with pomalidomide induced modest increases of HbF with similar efficacy as hydroxyurea. However, in stark contrast to hydroxyurea's myelosuppressive effects, pomalidomide augmented erythropoiesis and preserved bone marrow function. Surprisingly, combinatory therapy with both drugs failed to mitigate hydroxyurea's myelotoxic effects and caused loss of HbF induction. These findings support further evaluation of pomalidomide as a novel therapy for SCD.

Original languageEnglish (US)
Pages (from-to)1109-1112
Number of pages4
JournalBlood
Volume118
Issue number4
DOIs
StatePublished - Jul 28 2011

Fingerprint

Fetal Hemoglobin
Hydroxyurea
Sickle Cell Anemia
Erythropoiesis
Thalidomide
Thalassemia
Hematologic Neoplasms
Pharmaceutical Preparations
Transgenic Mice
pomalidomide
Bone
Hemoglobins
Stem Cells
Bone Marrow
Therapeutics

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Pomalidomide augments fetal hemoglobin production without the myelosuppressive effects of hydroxyurea in transgenic sickle cell mice. / Meiler, Steffen E; Wade, Marlene; Kutlar, Ferdane; Yerigenahally, Shobha D.; Xue, Yongjun; Moutouh-de Parseval, Laure A.; Corral, Laura G.; Swerdlow, Paul S.; Kutlar, Abdullah.

In: Blood, Vol. 118, No. 4, 28.07.2011, p. 1109-1112.

Research output: Contribution to journalArticle

Meiler, SE, Wade, M, Kutlar, F, Yerigenahally, SD, Xue, Y, Moutouh-de Parseval, LA, Corral, LG, Swerdlow, PS & Kutlar, A 2011, 'Pomalidomide augments fetal hemoglobin production without the myelosuppressive effects of hydroxyurea in transgenic sickle cell mice', Blood, vol. 118, no. 4, pp. 1109-1112. https://doi.org/10.1182/blood-2010-11-319137
Meiler, Steffen E ; Wade, Marlene ; Kutlar, Ferdane ; Yerigenahally, Shobha D. ; Xue, Yongjun ; Moutouh-de Parseval, Laure A. ; Corral, Laura G. ; Swerdlow, Paul S. ; Kutlar, Abdullah. / Pomalidomide augments fetal hemoglobin production without the myelosuppressive effects of hydroxyurea in transgenic sickle cell mice. In: Blood. 2011 ; Vol. 118, No. 4. pp. 1109-1112.
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