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IN UTERO ORIGIN OF MYELOFIBROSIS PRESENTING IN ADULT MONOZYGOTIC TWINS AFTER A PROLONGED DISEASE LATENCY

ABSTRACT: The latency between initiating somatic cancer driver mutation acquisition by a single cell and clinical presentation is largely unknown. We present a remarkable case of monozygotic twins presenting with CALR mutation-positive myeloproliferative neoplasms (MPNs) aged 37 and 38. Whole genome sequencing lineage-tracing revealed a common clonal origin of the CALR-mutant MPN clone, which occurred in utero followed by twin-to-twin transplacental transmission. Index sorting and single-colony genotyping revealed phenotypic hematopoietic stem cells (HSCs) as the likely MPN-propagating cell. This case provides a unique window into the prolonged evolutionary dynamics of MPNs and fitness advantage exerted by MPN-associated driver mutations in HSCs.

PROVIDER: EGAS00001005744 | EGA |

REPOSITORIES: EGA

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