Sickle cell disease and acute leukemia: one case report and an extensive review

Abstract

Population-based studies and case reports suggest that there may be an increased risk of acute leukemia associated with sickle cell disease (SCD). Following the description of a new case report, an extensive review of the literature identified 51 previously described cases. Most cases study showed myelodysplastic features confirmed, when available, by genetic markers such as chromosome 5 and/or chromosome 7 abnormalities and TP53 gene mutations. The increased risk of leukemogenesis is certainly multifactorial and related to the pathophysiologic mechanisms of the clinical manifestations of SCD. Chronic hemolysis and secondary hemochromatosis may cause increased chronic inflammation, resulting in persistent marrow stress, which could potentially compromise the genomic stability of the hematopoietic stem cells generating genomic damage and somatic mutations over the course of SCD and its treatment, resulting in a clone that led to acute myeloid leukemia.

Hematological Malignancies in Sickle Cell Disease Patients: Report of Four Cases in Togo and Literature Review

“…Hemopathies can develop during all major forms of sickle cell disease. Acute leukemia has been described in all these major forms in France [6]. The homozygous SS form was the most common in our series.…”

“…Olena O Seminog and al in England, in a study of administrative data, showed that within the black race, major sickle cell patients had a higher risk of developing cancer than a control cohort for cancers in general and particularly for hematological malignancies, but also for certain solid tumors [15]. In fact, the risk of hematological malignancy in sickle cell disease is 2 to 11 times as high as in the general population [6]. In fact, the increased risk of leukemogenesis in major sickle cell disease is thought to be multifactorial.…”

“…In fact, the increased risk of leukemogenesis in major sickle cell disease is thought to be multifactorial. Chronic hemolysis and secondary hemochromatosis could cause increased chronic inflammation, leading to persistent bone mar-row stress, which could be at the origin of genetic instability of hematopoietic stem cells, generating genomic damage and somatic mutations during the course of sickle cell disease [6]. Long-term hydroxyurea has been suggested by some authors as an etiological factor in the occurrence of hematological malignancies in SCD.…”

“…Indeed, the increased risk of leukemogenesis is thought to be multifactorial and linked to the pathophysiological mechanisms of the clinical manifestations of sickle cell disease. Chronic hemolysis and secondary hemochromatosis may cause increased chronic inflammation, leading to persistent bone marrow stress, which could be at the origin of genetic instability of hematopoietic stem cells, generating genomic damage and somatic mutations during the course of sickle cell disease [6]. The first description of the coexistence of SCD with acute myeloid leukemia (AML) was reported by Goldin and al.…”

“…in 1953 in a 38-year-old black man [7]. Subsequently, several Western [4] [6] and African [8] [9] studies have reported hematological malignancies during SCD, and a synthesis of some 30 studies reporting 52 cases together was made by Giovanna Cannas and al in 2023 [6].…”