ENPP4 and HOXA3 as potential leukaemia stem cell markers in acute myeloid leukaemia

Introduction: Acute myeloid leukaemia (AML) is a heterogeneous malignant disease with a high degree of treatment failure using chemotherapy. Leukaemia stem cells (LSCs) are CD34+CD38- early progenitors associated with poor prognosis in AML. A unique LSC phenotype that excludes rare normal haematopoi...

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Main Authors: Mohd Amin, A, Panneerselvan, N, Md Noor, S, Mohtaruddin, N, Sathar, J, Norbaya, WS, Osman, R, Kee, LH, Mohd Yaaku, WH, Cheong, SK, Abdullah, M
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Published: Malaysian Society of Pathologists 2023
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author Mohd Amin, A
Panneerselvan, N
Md Noor, S
Mohtaruddin, N
Sathar, J
Norbaya, WS
Osman, R
Kee, LH
Mohd Yaaku, WH
Cheong, SK
Abdullah, M
author_facet Mohd Amin, A
Panneerselvan, N
Md Noor, S
Mohtaruddin, N
Sathar, J
Norbaya, WS
Osman, R
Kee, LH
Mohd Yaaku, WH
Cheong, SK
Abdullah, M
author_sort Mohd Amin, A
collection UPM
description Introduction: Acute myeloid leukaemia (AML) is a heterogeneous malignant disease with a high degree of treatment failure using chemotherapy. Leukaemia stem cells (LSCs) are CD34+CD38- early progenitors associated with poor prognosis in AML. A unique LSC phenotype that excludes rare normal haematopoietic stem cells (HSC) is still elusive. This study aimed to determine expression of selected potential LSC markers in normal and leukaemic myeloid cells and correlate prognosis in AML patients. Materials and methods: Flow cytometry and RT-qPCR measured expressions of ALDH, IL3RA/CD123, CLEC12A/CLL-1/CD371, HOXA3 and ENPP4. Normal cord blood (n=3) and blood monocytes (n=5) represented HSC and mature cells, respectively. Myeloid leukaemia cell lines (THP-1, KG-1a, K562 and HL-60) represented progenitor cells at various stages of maturation. AML samples included chemo-resistant (n=8), early relapse (n=2) and late relapse (n=18). Results: Combining protein/gene expressions, CD34+CD38- was a feature of immature cells seen in cord blood, KG-1a, and K562 but not more mature cells (blood monocytes and HL-60). Normal cells expressed CD371 while mature cells (blood monocytes and HL-60) lacked CD123. ENPP4 was not expressed on normal cells while HOXA3 was expressed only on cord blood and THP-1. In AML, CD123, HOXA3, ENPP4 (but not CD371) were significantly increased in the CD34+CD38- fraction of chemo-resistant patients while ALDH was associated with chemo-resistance. Conclusion: CD34+CD38- presented an immature phenotype and with ALDH were associated with poor prognosis. CD123, HOXA3 and ENPP4 further enriched the LSC population. ENPP4 has not been reported and has the advantage of not being expressed on HSC and normal monocytes.
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spelling upm.eprints-1077152024-10-28T02:45:35Z http://psasir.upm.edu.my/id/eprint/107715/ ENPP4 and HOXA3 as potential leukaemia stem cell markers in acute myeloid leukaemia Mohd Amin, A Panneerselvan, N Md Noor, S Mohtaruddin, N Sathar, J Norbaya, WS Osman, R Kee, LH Mohd Yaaku, WH Cheong, SK Abdullah, M Introduction: Acute myeloid leukaemia (AML) is a heterogeneous malignant disease with a high degree of treatment failure using chemotherapy. Leukaemia stem cells (LSCs) are CD34+CD38- early progenitors associated with poor prognosis in AML. A unique LSC phenotype that excludes rare normal haematopoietic stem cells (HSC) is still elusive. This study aimed to determine expression of selected potential LSC markers in normal and leukaemic myeloid cells and correlate prognosis in AML patients. Materials and methods: Flow cytometry and RT-qPCR measured expressions of ALDH, IL3RA/CD123, CLEC12A/CLL-1/CD371, HOXA3 and ENPP4. Normal cord blood (n=3) and blood monocytes (n=5) represented HSC and mature cells, respectively. Myeloid leukaemia cell lines (THP-1, KG-1a, K562 and HL-60) represented progenitor cells at various stages of maturation. AML samples included chemo-resistant (n=8), early relapse (n=2) and late relapse (n=18). Results: Combining protein/gene expressions, CD34+CD38- was a feature of immature cells seen in cord blood, KG-1a, and K562 but not more mature cells (blood monocytes and HL-60). Normal cells expressed CD371 while mature cells (blood monocytes and HL-60) lacked CD123. ENPP4 was not expressed on normal cells while HOXA3 was expressed only on cord blood and THP-1. In AML, CD123, HOXA3, ENPP4 (but not CD371) were significantly increased in the CD34+CD38- fraction of chemo-resistant patients while ALDH was associated with chemo-resistance. Conclusion: CD34+CD38- presented an immature phenotype and with ALDH were associated with poor prognosis. CD123, HOXA3 and ENPP4 further enriched the LSC population. ENPP4 has not been reported and has the advantage of not being expressed on HSC and normal monocytes. Malaysian Society of Pathologists 2023 Article PeerReviewed Mohd Amin, A and Panneerselvan, N and Md Noor, S and Mohtaruddin, N and Sathar, J and Norbaya, WS and Osman, R and Kee, LH and Mohd Yaaku, WH and Cheong, SK and Abdullah, M (2023) ENPP4 and HOXA3 as potential leukaemia stem cell markers in acute myeloid leukaemia. Malaysian Journal of Pathology, 45 (1). pp. 65-76. ISSN 0126-8635 https://openurl.ebsco.com/EPDB%3Agcd%3A15%3A29989151/detailv2?sid=ebsco%3Aocu%3Arecord&id=ebsco%3Agcd%3A163418079&bquery=IS%200126-8635%20AND%20VI%2045%20AND%20IP%201%20AND%20DT%202023&page=1
spellingShingle Mohd Amin, A
Panneerselvan, N
Md Noor, S
Mohtaruddin, N
Sathar, J
Norbaya, WS
Osman, R
Kee, LH
Mohd Yaaku, WH
Cheong, SK
Abdullah, M
ENPP4 and HOXA3 as potential leukaemia stem cell markers in acute myeloid leukaemia
title ENPP4 and HOXA3 as potential leukaemia stem cell markers in acute myeloid leukaemia
title_full ENPP4 and HOXA3 as potential leukaemia stem cell markers in acute myeloid leukaemia
title_fullStr ENPP4 and HOXA3 as potential leukaemia stem cell markers in acute myeloid leukaemia
title_full_unstemmed ENPP4 and HOXA3 as potential leukaemia stem cell markers in acute myeloid leukaemia
title_short ENPP4 and HOXA3 as potential leukaemia stem cell markers in acute myeloid leukaemia
title_sort enpp4 and hoxa3 as potential leukaemia stem cell markers in acute myeloid leukaemia
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