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KMID : 0338420210360020401
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The Korean Journal of Internal Medicine
2021 Volume.36 No. 2 p.401 ~ p.412
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Leukemic stem cell phenotype is associated with mutational profile in acute myeloid leukemia
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Han Hee-Joo
Byun Ja-Min
Shin Dong-Yeop
Yoon Sung-Soo
Koh Young-Il
Hong Jun-Shik
Kim In-Ho
Lee Chan-Sup
Yoo Hyeon-Joo
Yun Hong-Seok
Kim Man-Jin
Cho Sung-Im
Seong Moon-Woo
Park Sung-Sup
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Abstract
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Background/Aims: Understanding leukemic stem cell (LSC) is important for acute myeloid leukemia (AML) treatment. However, association of LSC with patient prognosis and genetic information in AML patients is unclear.
Methods: Here we investigated the associations between genetic information and the various LSC phenotypes, namely multipotent progenitor (MPP)-like, lymphoid primed multipotent progenitor (LMPP)-like and granulocyte-macrophage progenitors (GMP)-like LSC in 52 AML patients.
Results: In secondary AML patients, MPP-like LSC was significantly higher than de novo AML (p = 0.0037). The proportion of MPP-like LSC was especially high in post-myeloproliferative neoplasm AML (p = 0.0485). There was no correlation between age and LSC phenotype. Mutations of KRAS and NRAS were observed in MPP-like LSC dominant patients, TP53 and ASXL1 mutations in LMPP-like LSC dominant patients, and CEBPA, DNMT3A and IDH1 mutations in GMP-like LSC dominant patients. Furthermore, KRAS mutation was significantly associated with MPP-like LSC expression (p = 0.0540), and TP53 mutation with LMPP-like LSC expression (p = 0.0276). When the patients were separated according to the combined risk including next generation sequencing data, the poorer the prognosis, the higher the LMPP-like LSC expression (p = 0.0052). This suggests that the dominant phenotype of LSC is one of the important factors in predicting the prognosis and treatment of AML.
Conclusions: LSC phenotype in AML is closely associated with the recurrent mutations which has prognostic implication. Further research to confirm the meaning of LSC phenotype in the context of genetic aberration is warranted.
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KEYWORD
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Acute myeloid leukemia, Leukemic stem cell, Next generation sequencing, Prognosis
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