ASH 2022 | The prognostic value of structural heterogeneity of chromosome 1q in multiple myeloma
Gareth Morgan, MD, PhD, FRCP, FRCPath, NYU Langone, New York City, NY, discusses a study that utilized chromosomal mapping techniques to determine the aberrant transcriptional landscape of 1q in patients with newly diagnosed multiple myeloma. Overall, the data showed that 1q is associated with an adverse outcome and an aggressive disease phenotype. Patients with focal gains were associated with favorable outcomes, while those with arm-length gains were associated with high-risk disease features and aggressive clinical behavior. From this data, Prof. Morgan believes that whole arm-length gains in chromosome 1q is an improtant prognostic factor in determining whether a patient has low- or high-risk disease. This interview took place at the 64th ASH Annual Meeting and Exposition congress in New Orleans, LA.
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Transcript (edited for clarity)
There’s a really important prognostic factor in myeloma, and it’s either loss of the short arm of chromosome 1 or gain of the long arm of chromosome 1. So we’ve had a presentation here about the prognostic value of the long arm. And so we really studied it in depth and mapped the chromosome up and down in many hundreds of patients to see if we could find specific regions with genes within them, that altered prognosis that we could use as targets for therapy...
There’s a really important prognostic factor in myeloma, and it’s either loss of the short arm of chromosome 1 or gain of the long arm of chromosome 1. So we’ve had a presentation here about the prognostic value of the long arm. And so we really studied it in depth and mapped the chromosome up and down in many hundreds of patients to see if we could find specific regions with genes within them, that altered prognosis that we could use as targets for therapy. It turned out that one third of the cases had focal lesions, and you could group those into maybe four or five specific regions of chromosome 1. And the one at q21 was the most important. And we found a number of drivers within there, including MCL1, which you can target potentially. But the most important message was it’s not those focal regions that impact prognosis, it’s gain of the whole arm. And of course, you can have multiple copies of the whole arm and have amplification. And what that I think does is not just alter the gene dosage on chromosome 1, but it’s clear it affects the structure of the nucleus enough to deregulate thousands of other genes. And so the message for clinicians is, don’t look at the focal events, look for whole-arm gain and more than three copies of the whole arm. And then you have a very good prognostic factor that can help you determine whether patients have low or high-risk disease.
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