Occurrence of acute myeloid leukemia in hydroxyurea-treated sickle cell disease patient

Cancer Biol Ther. 2019;20(11):1389-1397. doi: 10.1080/15384047.2019.1647055. Epub 2019 Aug 18.

Abstract

Hydroxyurea (HU) has been widely used in sickle cell disease. Its potential long-term risk for carcinogenesis or leukemogenic risk remains undefined. Here, we report a 26 y old African-American female with Sickle Cell Disease (SCD) who developed refractory/relapsed acute myeloid leukemia (AML) 6 months after 26 months of HU use. That patient's cytogenetics and molecular genetics analyses demonstrated a complex mutation profile with 5q deletion, trisomy 8, and P53 deletion (deletion of 17p13.1). P53 gene sequence studies revealed a multitude of somatic mutations that most suggest a treatment-related etiology. The above-mentioned data indicates that the patient may have developed acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) as a direct result of HU exposure.

Keywords: Hydroxyurea; P53 gene; acute myeloid leukemia with myelodysplasia-related changes; sickle cell disease.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anemia, Sickle Cell / complications
  • Anemia, Sickle Cell / drug therapy*
  • Anemia, Sickle Cell / epidemiology
  • Anemia, Sickle Cell / pathology
  • Carcinogenesis / drug effects*
  • Carcinogenesis / genetics
  • Chromosome Deletion
  • Chromosomes, Human, Pair 17 / drug effects
  • Chromosomes, Human, Pair 5 / drug effects
  • Chromosomes, Human, Pair 8 / drug effects
  • Female
  • Humans
  • Hydroxyurea / adverse effects*
  • Hydroxyurea / therapeutic use
  • Leukemia, Myeloid, Acute / chemically induced
  • Leukemia, Myeloid, Acute / epidemiology
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / pathology
  • Mutation / drug effects
  • Risk Factors

Substances

  • Hydroxyurea