Our study on chromosome shattering in acute myeloid leukemia (AML), so-called chromothripsis, got published in Haematologica!

Somatic aberrations are causal drivers of leukemia and constitute changes such as the substitution, deletion, gain or rearrangement of DNA. While most AML patients carry more than one such mutation, they tend to include at most one larger rearrangement per case, in combination with one or more smaller changes (although of course this does not limit the detrimental effects and consequences that follow). In contrast, the subgroup of complex-karyotype (CK) AMLs harbors a surprising number of very large and seemingly unrelated aberrations, including the loss and gain of multiple chromosomes. Notably, CK-AML cells not only remain viable but outcompete healthy cells of the blood and bone marrow and frequently even continue to thrive under intensive chemotherapy. CK-AML patients therefore typically face a poor prognosis. However, how such massive changes can accumulate in these cells and how they cooperate to drive leukemic transformation is still largely unclear - questions that must be answered to develop rational new strategies for patient care.

We therefore set out to study chromothripsis, or chromosome-shattering, in a large cohort of CK-AML patients: The simultaneous shattering of one or more chromosomes, followed by the erroneous ligation and repair of the resulting DNA fragments, has been described in other cancers before and can lead to a large number of oscillating DNA gains and losses.

In the aforementioned article we describe our findings from an integrative analysis on the frequency of chromothripsis in CK-AML, the landscape of affected chromosomes, the associated gene expression and signaling pathway deregulation and correlations with clinical data.