Poor mobilization of autologous CD34+ peripheral blood stem cells in haematology patients undergoing autologous stem cell transplantation is associated with the presence of variants in genes implicated in clonal haematopoiesis of indeterminant potential

Grace Gifford; Luke Hesson; Jason W H Wong; Adam Carroll; Sara Gabrielli; LiJun Bai; Wei Xia; William Stevenson; Matthew Greenwood

doi:10.1111/bjh.17316

Poor mobilization of autologous CD34⁺ peripheral blood stem cells in haematology patients undergoing autologous stem cell transplantation is associated with the presence of variants in genes implicated in clonal haematopoiesis of indeterminant potential

Br J Haematol. 2021 May;193(4):841-844. doi: 10.1111/bjh.17316. Epub 2021 Jan 22.

Authors

Grace Gifford^{1

2}, Luke Hesson^{3

4

5}, Jason W H Wong⁶, Adam Carroll⁷, Sara Gabrielli², LiJun Bai^{1

8}, Wei Xia^{1

8}, William Stevenson^{1

2

9}, Matthew Greenwood^{1

8}

Affiliations

¹ Department of Haematology and Transfusion, Royal North Shore Hospital, St Leonards, Australia.
² Northern Blood Research Centre, Kolling Institute of Medical Research, St Leonards, Australia.
³ Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Darlinghurst, Australia.
⁴ Clinical Genetics, Douglass Hanly Moir Pathology, Dubbo, Australia.
⁵ Faculty of Medicine, Prince of Wales Clinical School, University of New South Wales, Kensington, Australia.
⁶ School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China.
⁷ Northern Clinical School, The University of Sydney, Sydney, Australia.
⁸ Cellular Therapeutic Research Laboratory, Northern Blood Research Centre, Kolling Institute of Medical Research, St Leonards, Australia.
⁹ Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.

PMID: 33481245
DOI: 10.1111/bjh.17316

Abstract

Clonal haematopoiesis of indeterminant potential (CHIP) increases in frequency with age. The effect of CHIP on the mobilization of autologous CD34+ peripheral blood stem cells (PBSC) has not been reported. This study uses a DNA-based targeted candidate gene approach to identify the presence of somatic mutations in ASXL1, DNMT3A, JAK2, SF3B1, TET2 and TP53 in CD34+ haematopoietic progenitor cell-apheresis products of 96 patients who undergo PBSC mobilization for autologous stem cell transplantation (ASCT). Variants were identified in a significantly greater proportion of patients who experience poor CD34+ PBSC mobilization. A DNA-based targeted candidate gene array is able to predict poor CD34+ PBSC mobilization and may be deployed pre-emptively to minimize mobilization and graft failures.

Keywords: clonality; haematopoietic stem cells; molecular; stem cell mobilization/homing.

MeSH terms

Adult
Age Factors
Aged
Autografts
Clonal Hematopoiesis / genetics*
Female
Hematopoietic Stem Cell Mobilization*
Humans
Male
Middle Aged
Mutation*
Oligonucleotide Array Sequence Analysis*
Peripheral Blood Stem Cell Transplantation*
Peripheral Blood Stem Cells*