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. 2021 Sep;100(9):2207-2214.
doi: 10.1007/s00277-021-04550-8. Epub 2021 May 15.

Multiplex ligation-dependent probe amplification identifies copy number changes in normal and undetectable karyotype MDS patients

Jing Ma #  1 , Xiaofei Ai #  2 , Jinhuan Wang #  3 , Limin Xing  4 , Chen Tian  1 , Hongliang Yang  1 , Yong Yu  1 , Haifeng Zhao  1 , Xiaofang Wang  1 , Zhigang Zhao  5 , Yafei Wang  6 , Zeng Cao  7
Affiliations

Multiplex ligation-dependent probe amplification identifies copy number changes in normal and undetectable karyotype MDS patients

Jing Ma et al. Ann Hematol. 2021 Sep.

Abstract

Chromosomal abnormalities play an important role in classification and prognostication of myelodysplastic syndrome (MDS) patients. However, more than 50% of low-risk MDS patients harbor a normal karyotype. Recently, multiplex ligation-dependent probe amplification (MLPA) has emerged as an effective and robust method for the detection of cytogenetic aberrations in MDS patients. To characterize the subset of MDS with normal karyotype or failed chromosome banding analysis, we analyzed 144 patient samples with normal karyotype or undetectable through regular chromosome banding analysis, which were subjected to parallel comparison via fluorescence in situ hybridization (FISH) and MLPA. MLPA identifies copy number changes in 16.7% of 144 MDS patients, and we observed a significant difference in overall survival (OS) (median OS: undefined vs 27 months, p=0.0071) in patients with normal karyotype proved by MLPA versus aberrant karyotype cohort as determined by MLPA. Interestingly, patients with undetectable karyotype via regular chromosome banding indicated inferior outcome. Collectively, MDS patients with normal or undetectable karyotype via chromosome banding analysis can be further clarified by MLPA, providing more prognostic information that benefit for individualized therapy.

Keywords: Cytogenetic analysis; Multiplex ligation-dependent probe amplification; Normal karyotype; Myelodysplastic syndromes; Undetectable chromosome pattern.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Diagnostic approach in 258 MDS patients. Distribution of patients with aberrant karyotype, normal cytogenetics, and failed chromosome banding analysis is depicted
Fig. 2
Fig. 2
OS analysis of patients harboring aberration (n=24) or not detected (n=120 ) by MLPA in 144 MDS patients with normal and failed karyotype
Fig. 3
Fig. 3
OS of patients with normal karyotype (n=132) and failed chromosome banding analysis (n=12)
Fig. 4
Fig. 4
OS of patients with cytogenetic aberrations detected using MLPA compared with other patients in lower risk IPSS-R group (a MLPA+:n=5, MLPA-:n=68) and higher risk IPSS-R group (b MLPA+:n=19, MLPA-:n=52)
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