Ann Lab Med.  2018 Nov;38(6):495-502. 10.3343/alm.2018.38.6.495.

Poor Prognostic Implication of ASXL1 Mutations in Korean Patients With Chronic Myelomonocytic Leukemia

• Kim HY
• Lee KO
• Park S
• Jang JH
• Jung CW
• Kim SH
• Kim HJ

• KMID: 2429113
• DOI: http://doi.org/10.3343/alm.2018.38.6.495

Abstract

BACKGROUND
Molecular genetic abnormalities are observed in over 90% of chronic myelomonocytic leukemia (CMML) cases. Recently, several studies have demonstrated the negative prognostic impact of ASXL1 mutations in CMML patients. We evaluated the prognostic impact of ASXL1 mutations and compared five CMML prognostic models in Korean patients with CMML.
METHODS
We analyzed data from 36 of 57 patients diagnosed as having CMML from January 2000 to March 2016. ASXL1 mutation analysis was performed by direct sequencing, and the clinical and laboratory features of patients were compared according to ASXL1 mutation status.
RESULTS
ASXL1 mutations were detected in 18 patients (50%). There were no significant differences between the clinical and laboratory characteristics of ASXL1-mutated (ASXL1+) CMML and ASXL1-nonmutated (ASXL1−) CMML patients (all P>0.05). During the median follow-up of 14 months (range, 0-111 months), the overall survival (OS) of ASXL1+ CMML patients was significantly inferior to that of ASXL1− CMML patients with a median survival of 11 months and 19 months, respectively (log-rank P=0.049). An evaluation of OS according to the prognostic models demonstrated inferior survival in patients with a higher risk category according to the Mayo molecular model (log-rank P=0.001); the other scoring systems did not demonstrate a significant association with survival.
CONCLUSIONS
We demonstrated that ASXL1 mutations, occurring in half of the Korean CMML patients examined, were associated with inferior survival. ASXL1 mutation status needs to be determined for risk stratification in CMML.

Keyword

Chronic myelomonocytic leukemia; ASXL1; Risk stratification; Prognostic models; Mayo molecular model; Korea

MeSH Terms

Follow-Up Studies
Humans
Korea
Leukemia, Myelomonocytic, Chronic*
Models, Molecular
Molecular Biology

Figure

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  Fig. 1 Kaplan-Meier plots of the (A) overall survival and (B) leukemic transformation-free survival in patients with chronic myelomonocytic leukemia according to ASXL1 mutation status.

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  Fig. 2 Kaplan-Meier plots of the overall survival in patients with chronic myelomonocytic leukemia according to the (A) Spanish cytogenetic risk stratification, (B) MDAPS, (C) GFM model, (D) Mayo model, and (E) Mayo molecular model.Abbreviations: MDAPS, MD Anderson prognostic scoring system; GFM, Groupe Français des Myélodysplasies.

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