CD45RA, a specific marker for leukaemia stem cell sub-populations in acute myeloid leukaemia
Bas Kersten
Department of Haematology, VU University Medical Centre, Amsterdam, the Netherlands
Both authors contributed equally.Search for more papers by this authorMatthijs Valkering
Department of Haematology, VU University Medical Centre, Amsterdam, the Netherlands
Both authors contributed equally.Search for more papers by this authorRolf Wouters
Department of Haematology, VU University Medical Centre, Amsterdam, the Netherlands
Search for more papers by this authorRosa van Amerongen
Department of Haematology, VU University Medical Centre, Amsterdam, the Netherlands
Search for more papers by this authorDiana Hanekamp
Department of Haematology, VU University Medical Centre, Amsterdam, the Netherlands
Search for more papers by this authorZinia Kwidama
Department of Haematology, VU University Medical Centre, Amsterdam, the Netherlands
Search for more papers by this authorPeter Valk
Department of Haematology, Erasmus Medical Centre, Rotterdam, the Netherlands
Search for more papers by this authorGert Ossenkoppele
Department of Haematology, VU University Medical Centre, Amsterdam, the Netherlands
Search for more papers by this authorWendelien Zeijlemaker
Department of Haematology, VU University Medical Centre, Amsterdam, the Netherlands
Search for more papers by this authorGertjan Kaspers
Department of Paediatric Oncology/Haematology, VU University Medical Centre, Amsterdam, the Netherlands
Search for more papers by this authorJacqueline Cloos
Department of Haematology, VU University Medical Centre, Amsterdam, the Netherlands
Department of Paediatric Oncology/Haematology, VU University Medical Centre, Amsterdam, the Netherlands
Both authors contributed equally.Search for more papers by this authorCorresponding Author
Gerrit J. Schuurhuis
Department of Haematology, VU University Medical Centre, Amsterdam, the Netherlands
Both authors contributed equally.Correspondence: Dr Gerrit J. Schuurhuis, Department of Haematology, VU University Medical Centre, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands
E-mail: [email protected]
Search for more papers by this authorBas Kersten
Department of Haematology, VU University Medical Centre, Amsterdam, the Netherlands
Both authors contributed equally.Search for more papers by this authorMatthijs Valkering
Department of Haematology, VU University Medical Centre, Amsterdam, the Netherlands
Both authors contributed equally.Search for more papers by this authorRolf Wouters
Department of Haematology, VU University Medical Centre, Amsterdam, the Netherlands
Search for more papers by this authorRosa van Amerongen
Department of Haematology, VU University Medical Centre, Amsterdam, the Netherlands
Search for more papers by this authorDiana Hanekamp
Department of Haematology, VU University Medical Centre, Amsterdam, the Netherlands
Search for more papers by this authorZinia Kwidama
Department of Haematology, VU University Medical Centre, Amsterdam, the Netherlands
Search for more papers by this authorPeter Valk
Department of Haematology, Erasmus Medical Centre, Rotterdam, the Netherlands
Search for more papers by this authorGert Ossenkoppele
Department of Haematology, VU University Medical Centre, Amsterdam, the Netherlands
Search for more papers by this authorWendelien Zeijlemaker
Department of Haematology, VU University Medical Centre, Amsterdam, the Netherlands
Search for more papers by this authorGertjan Kaspers
Department of Paediatric Oncology/Haematology, VU University Medical Centre, Amsterdam, the Netherlands
Search for more papers by this authorJacqueline Cloos
Department of Haematology, VU University Medical Centre, Amsterdam, the Netherlands
Department of Paediatric Oncology/Haematology, VU University Medical Centre, Amsterdam, the Netherlands
Both authors contributed equally.Search for more papers by this authorCorresponding Author
Gerrit J. Schuurhuis
Department of Haematology, VU University Medical Centre, Amsterdam, the Netherlands
Both authors contributed equally.Correspondence: Dr Gerrit J. Schuurhuis, Department of Haematology, VU University Medical Centre, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands
E-mail: [email protected]
Search for more papers by this authorAbstract
Chemotherapy resistant leukaemic stem cells (LSC) are thought to be responsible for relapses after therapy in acute myeloid leukaemia (AML). Flow cytometry can discriminate CD34+CD38− LSC and normal haematopoietic stem cells (HSC) by using aberrant expression of markers and scatter properties. However, not all LSC can be identified using currently available markers, so new markers are needed. CD45RA is expressed on leukaemic cells in the majority of AML patients. We investigated the potency of CD45RA to specifically identify LSC and HSC and improve LSC quantification. Compared to our best other markers (CLL-1, also termed CLEC12A, CD33 and CD123), CD45RA was the most reliable marker. Patients with high percentages (>90%) of CD45RA on CD34+CD38− LSC have 1·69-fold higher scatter values compared to HSC (P < 0·001), indicating a more mature CD34+CD38− phenotype. Patients with low (<10%) or intermediate (10–90%) CD45RA expression on LSC showed no significant differences to HSC (1·12- and 1·15-fold higher, P = 0·31 and P = 0·44, respectively). CD45RA-positive LSC tended to represent more favourable cytogenetic/molecular markers. In conclusion, CD45RA contributes to more accurate LSC detection and is recommended for inclusion in stem cell tracking panels. CD45RA may contribute to define new LSC-specific therapies and to monitor effects of anti-LSC treatment.
Supporting Information
| Filename | Description |
|---|---|
| bjh13941-sup-0001-SupInfo.docxWord document, 592.4 KB | Table SIA. FSC and SSC and FSC*SSC values for LSC and HSC/MPP in the CD45RAhigh group. Table SIB. FSC and SSC and FSC*SSC values for LSC and HSC/MPP in the CD45RAlow group. Table SIC. FSC and SSC and FSC*SSC values for LSC and HSC/MPP in the CD45RAint group. Table SII. Molecular make up of CD45RA defined sub-groups. Figure S1. CD45RA in NBM, three additional cases. Figure S2. Distribution of the scores per marker over the four performance groups. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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