This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: Researchers at the Leibniz Institute DSMZ-German Collection of Microorganisms and Cell Cultures have, for the first time, identified a model cell line for a rare form of acute myeloid leukemia (AML). "The KOPM-88 cell line is, to date, the first and only known cell line worldwide to carry the KMT2A::SEPTIN6 fusion gene," explains Dr.
Stefan Nagel, head of the Molecular Genetics research group in the Department of Human and Animal Cell Cultures at the DSMZ. "Thus, cancer research now has an urgently needed model system to specifically investigate this aggressive subtype of leukemia and develop novel therapeutic approaches." The work is published in the journal Cells. Fusion genes arise when chromosomes in cancer cells undergo abnormal rearrangements, causing parts of different genes to merge.
Such genetic alterations are particularly common in leukemias (blood cancer). These specific alterations help medical staff classify cancers more accurately and, in some cases, can also be targeted directly with treatment. The KMT2A gene plays a particular role in this context: It can fuse with more than 100 different partner genes, which can be divided into five groups.
Such KMT2A fusion genes are usually linked with a poor prognosis and have so far proved difficult to treat therapeutically. Appropriate model systems that enable the biological properties of these cancer types to be reproduced and studied in the laboratory are therefore all the more important. The fusion gene KMT2A::SEPTIN6 has been described in tumor cells from children with acute myeloid leukemia.
The KOPM-88 cell line was originally established from the peripheral blood of an 11-year-old boy with AML. The research team led by Nagel has now demonstrated that this exact cell line carries the rare KMT2A::SEPTIN6 fusion gene. Consequently, KOPM-88 is not only the first known cell line with this fusion gene, but it is also the only available cell line representative of group 3 KMT2A fusion genes.
This represents a significant advance for research, as this leukemia subtype can now be systematically studied in vitro for the first time. The results demonstrate that KMT2A::SEPTIN6 functionally differs from other KMT2A fusion genes. Whereas most KMT2A fusions typically activate specific target genes, the DSMZ researchers in Braunschweig observed the opposite in this case: The classic target gene HOXA7 was repressed rather than switched on.
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