Tokyo: Leukaemia is a popular term used to describe a type of blood cancer. However, leukaemia is classified into distinct categories based on the type of cell involved. Myeloid/natural killer (NK) cell precursor acute leukaemia (MNKPL) is a distinct form.
Because of its rarity, no consensus exists on the particular features required to clinically identify this condition. In a recent article published in Science Advances, researchers from Tokyo Medical and Dental University (TMDU) used a variety of methodologies to better characterise MNKPL's molecular profile and medication sensitivity.
MNKPL was initially proposed as a leukaemia subtype in 1997. Extramedullary involvement is one of the distinguishing features of MNKPL. It is common in Eastern Asian countries. Although the immunological characteristic of MNKPL has been studied earlier, a complete genetic characterisation of this cancer type has yet to be completed.
These details would contribute to better accurate diagnosis for patients, resulting in more suitable therapy recommendations. As a result, the TMDU group sought to examine MNKPL on a single-cell level.
"A single-cell exploration of MNKPL would not only help us better understand its clinical and genomic features, but also clarify the specific cellular origin of this disease," said Dr. Akira Nishimura, lead author of the study.
The team first used what is known as a multiomics approach to investigate MNKPL patient samples. They used various sequencing technologies to determine if there were any relevant mutations in specific genes, look for expression differences in certain signalling pathways at the RNA level, and examine any unique DNA methylation patterns.
"Our results demonstrate that MNKPL has molecular qualities that are distinct from other similar cancers, such as acute myeloid leukaemia, T-cell acute lymphoblastic leukaemia, and mixed-phenotype acute leukaemia," explained Dr Masatoshi Takagi, senior author. "Specific hallmarks of MNKPL include activation of the NOTCH1 and RUNX3, as well as lower expression of the BCL11B."
Further work at the single-cell level in MNKPL cells showed that NK cells and myeloid cells come from a common progenitor cell type.
The researchers also conducted in vitro drug sensitivity assays where they measured MNKPL cell responses to 79 individual anti-cancer drugs.
"We observed that MNKPL cells were highly sensitive to a drug called L-asparaginase, which has already shown clinical effectiveness for this disease," said Dr. Nishimura.
"Mechanistically, we found that this was from the low expression of asparagine synthetase, a quality that was distinct from other similar types of leukaemia." (ANI)
