11 March 2024

New techniques have improved understanding of the molecular profile and drug sensitivity of a rare form of leukaemia, researchers have reported.

A team from Tokyo Medical and Dental University, Japan, used a variety of technologies to better characterise myeloid/natural killer cell precursor acute leukaemia (MNKPL) at molecular level.

Because MNKPL is so rare, there is no consensus on the specific characteristics needed to clinically identify this disease, the researchers say.

Using a ‘multi-omics’ approach to investigate samples from people with MNKPL, the team set out to determine if there were any relevant mutations in specific genes, to look for expression differences in certain signalling pathways at the RNA level, and to examine any unique DNA methylation patterns.

Writing in Science Advances, they demonstrated that MNKPL has distinct molecular qualities from other types of leukaemia, with specific hallmarks of MNKPL including the activation of NOTCH1 and RUNX3, as well as lower expression of the BCL11B.

Further work at the single-cell level in MNKPL cells suggested that NK cells and myeloid cells come from a common progenitor cell type, and are not lymphoid-derived as previously thought.

The researchers also conducted in vitro drug sensitivity assays where they measured MNKPL cell responses to 79 individual anti-cancer drugs.

Lead author Dr Akira Nishimura said: “We observed that MNKPL cells were highly sensitive to a drug called L-asparaginase, which has already shown clinical effectiveness for this disease.

“Mechanistically, we found that this was from low expression of asparagine synthetase, a quality that was distinct from other similar types of leukaemia.”

The researchers hope their findings will help clinicians diagnose MNKPL more effectively and will enable them to select the most appropriate treatment.


Nishimura A, Yokoyama K, Naruto T, Yamagishi C, Imamura T, Nakazono H, Kimura S, Ito M, Sagisaka M, Tanaka Y, Piao J, Namikawa Y, Yanagimachi M, Isoda T, Kanai A, Matsui H, Isobe T, Sato-Otsubo A, Higuchi N, Takada A, Okuno H, Saito S, Karakawa S, Kobayashi S, Hasegawa D, Fujisaki H, Hasegawa D, Koike K, Koike T, Rai S, Umeda K, Sano H, Sekinaka Y, Ogawa A, Kinoshita A, Shiba N, Miki M, Kimura F, Nakayama H, Nakazawa Y, Taga T, Taki T, Adachi S, Manabe A, Koh K, Ishida Y, Takita J, Ishikawa F, Goto H, Morio T, Mizutani S, Tojo A, Takagi M.  (2023) “Myeloid/Natural Killer (NK) Cell Precursor Acute Leukemia as a Distinct Leukemia Type.” Science Advances, doi:10.1126/sciadv.adj4407.

Link: https://www.science.org/doi/10.1126/sciadv.adj4407

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