Using iPS cells generated from a patient with a myeloid neoplasm caused by a rare chromosomal rearrangement between the MECOM and MYC genes, a team of researchers led by Associate Professor Yoshinori Yoshida and Clinical Assistant Professor Kazuhisa Chonabayashi (Department of Growth and Differentiation) successfully modeled the cancer to gain a better understanding of its pathogenic mechanisms and test potential drug therapies. There are many causes for cancers, but a primary means for their development is the rearrangement of chromosomes that allows cancer-causing genes to hijack enhancer elements from other genes to increase their expression aberrantly. For example, recurrent rearrangements on chromosome 3 (inv(3)(q21.
3q26.2) or t(3;3)(q21.3;q26.
2)) place a GATA2 enhancer close to the MECOM (EVI1) promoter to drive hematological malignancies by aberrantly enhancing MECOM gene expression. More recently, a specific type of leukemia, known as myelodysplastic syndromes (MDS)/ acute myeloid leukemia (AML) with atypical 3q26 rearrangements including t(3;8)(q26.2;q24), in which chromosomal changes also result in abnormally high expression of MECOM was characterized.
While these chromosomal rearrangements are rare, the resulting cancer has a poor prognosis with a median survival of only about six months and, as such, was designated as a new category of AML with MECOM rearrangement by the World Health Organization in 2022. To gain insights into this newly categorized disease and id.