MLPA and digitalMLPA in Pediatric Acute Lymphoblastic Leukemia
A study published in Modern Pathology by researchers from Semmelweis University (Budapest, Hungary), in collaboration with scientists from MRC Holland, utilised MLPA and digitalMLPA in combination with DNA and RNA sequencing to extensively characterise a nationwide cohort of 192 pediatric acute lymphoblastic leukemia (ALL) patients. ALL is the most common childhood malignancy, and while survival rates have significantly improved in the last years, disease progression and relapse remain challenging.
Using three conventional MLPA assays and one digitalMLPA probemix in combination with advanced sequencing, they were able to identify recurrent, subtype-specific genetic alterations that correlated with a certain relapse risk assessment profile. Conventional MLPA assays, which target a limited number of genes and regions associated with ALL, were sufficient to identify copy number alterations (CNAs) in the majority of samples tested. Given the extensive number of target probes included in D007 Acute Lymphoblastic Leukemia, digitalMLPA was able to detect additional CNAs in a number of samples. Next to the detailed exon-level investigation of copy number changes in ALL-related genes, digitalMLPA facilitated the identification of whole chromosome aberrations and large CNAs which other techniques are not suitable for and which would otherwise have gone undetected.
The authors propose that a combined approach involving digitalMLPA and targeted RNA sequencing has the potential to serve as an alternative to current time-consuming and labour-intensive workflows for the robust and comprehensive molecular characterization of complex ALL genotypes.
Probemixes used to analyse ALL in this study:
P327 iAMP21-ERG
P335 ALL-IKZF1
P383 T-ALL
D007 Acute Lymphoblastic Leukemia - version B1 was recently released with expanded coverage of ALL-relevant regions.