Stem cell mutations can be detected in myeloma patients years before onset of secondary leukemias

Ashwin Sridharan, Carolina D. Schinke, George Georgiev, Mariana da Silva Ferreira, Victor Thiruthuvanathan, Ian MacArthur, Tushar D. Bhagat, Gaurav S. Choudhary, Srinivas Aluri, Jiahao Chen, Kith Pradhan, Yu Xia, Maya Panjikaran, Gregory Sims, Chirag K. Bhagat, Ryan Bender, Lauryn Keeler, Armin Graber, Christoph Heuck, Frederick A. FletcherDaisy Alapat, Niels Weinhold, Sarah K. Johnson, Amittha Wickrema, Bart Barlogie, Gareth J. Morgan, Aditi Shastri, Ulrich Steidl, Britta Will, Amit Verma

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Therapy-related acute myeloid leukemia and myelodysplastic syndromes (t-AML/t-MDS) are secondary hematologic malignancies associated with poor prognosis, warranting insights into their predisposing conditions and cells of origin. We identified patients with myeloma who developed t-AML/t-MDS and analyzed their stem and progenitor cells collected years before the onset of secondary disease. We demonstrate that aberrant stem cells with high CD123 expression can be detected long before the onset of overt leukemia. Rigorous sorting, followed by targeted sequencing, resulted in ultradeep functional depth of sequencing and revealed preexisting mutant hematopoietic stem cell (HSC) clones, mainly harboring TP53 mutations, that became the dominant population at the time of leukemic presentation. Taken together, these data show that HSCs can act as reservoirs for leukemia-initiating cells many years before the onset of myeloid leukemia.

Original languageEnglish
Pages (from-to)3962-3967
Number of pages6
JournalBlood advances
Issue number23
StatePublished - 2019
Externally publishedYes


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