Impaired myelopoiesis in congenital neutropenia: insights into clonal and malignant hematopoiesis

Hematology Am Soc Hematol Educ Program. 2021 Dec 10;2021(1):514-520. doi: 10.1182/hematology.2021000286.


A common feature of both congenital and acquired forms of bone marrow failure is an increased risk of developing acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Indeed, the development of MDS or AML is now the major cause of mortality in patients with congenital neutropenia. Thus, there is a pressing clinical need to develop better strategies to prevent, diagnose early, and treat MDS/AML in patients with congenital neutropenia and other bone marrow failure syndromes. Here, we discuss recent data characterizing clonal hematopoiesis and progression to myeloid malignancy in congenital neutropenia, focusing on severe congenital neutropenia (SCN) and Shwachman-Diamond syndrome. We summarize recent studies showing excellent outcomes after allogenic hematopoietic stem cell transplantation for many (but not all) patients with congenital neutropenia, including patients with SCN with active myeloid malignancy who underwent transplantation. Finally, we discuss how these new data inform the current clinical management of patients with congenital neutropenia.

Publication types

  • Case Reports

MeSH terms

  • Child, Preschool
  • Clonal Hematopoiesis
  • Congenital Bone Marrow Failure Syndromes / complications*
  • Congenital Bone Marrow Failure Syndromes / physiopathology
  • Congenital Bone Marrow Failure Syndromes / therapy
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Infant
  • Leukemia, Myeloid, Acute / etiology*
  • Leukemia, Myeloid, Acute / physiopathology
  • Leukemia, Myeloid, Acute / therapy
  • Middle Aged
  • Myelodysplastic Syndromes / etiology*
  • Myelodysplastic Syndromes / physiopathology
  • Myelodysplastic Syndromes / therapy
  • Myelopoiesis*
  • Neutropenia / complications
  • Neutropenia / congenital*
  • Neutropenia / physiopathology
  • Neutropenia / therapy
  • Shwachman-Diamond Syndrome / complications
  • Shwachman-Diamond Syndrome / physiopathology
  • Shwachman-Diamond Syndrome / therapy

Supplementary concepts

  • Neutropenia, Severe Congenital, Autosomal Recessive 3