"Our results finally answer the common question posed by patients, 'How long has this cancer been growing?' as we were able to study how these particular cancers developed over the entire lifetime of individual patients," Dr. Jyoti Nangalia of the Wellcome Sanger Institute and the University of Cambridge, in the U.K., said in a news release.
She presented the study at the American Society of Hematology (ASH) virtual annual meeting.
In most patients, myeloproliferative neoplasms are driven by a genetic mutation called JAK2-V617F. By assessing this mutation and other cancer-related mutations, the researchers were able to trace the ancestry of different blood cells and estimate the time at which each patient acquired JAK2-V617F and other mutations.
They analyzed bone marrow and blood samples from 10 patients who developed Philadelphia-negative myeloproliferative neoplasms between age 20 and 76 years.
They found that the JAK2-V617F mutation was acquired in utero or in early childhood in all 10 patients in whom this mutation was the first or the only driver mutation.
The earliest age estimates for mutation acquisition was within a few weeks after conception and the upper estimate of age at acquisition was between 4.1 months and 11.4 years. The mean time between JAK2-V617F acquisition and disease presentation was 34 years.
"We were not expecting this. In fact, in one patient, the JAK2 mutation was acquired more than 50 years before their diagnosis," Dr. Nangalia said in the release.
This study shows that myeloproliferative neoplasms "originate from driver mutation acquisition very early in life, even before birth, with life-long clonal expansion and evolution, establishing a new paradigm for blood cancer development," the researchers write in their conference abstract.
"Early detection of mutant-JAK2 together with determination of clonal expansion rates could provide opportunities for early interventions aimed at minimizing thrombotic risk and targeting the mutant clone in at risk individuals," they add.
"The results suggests that there may be untapped opportunities to detect these conditions much earlier than previously and potentially intervene and prevent disease development," Dr. Robert Brodsky, with Johns Hopkins School of Medicine, Baltimore, Maryland, said during a briefing with reporters.
SOURCE: https://bit.ly/3abGyvN American Society of Hematology 2020 Annual Meeting, presented December 2, 2020.
By Megan Brooks
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