Feasibility of monitoring peripheral blood to detect emerging clones in children with acute lymphoblastic leukemia†
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Feasibility of monitoring peripheral blood to detect emerging clones in children with acute lymphoblastic leukemia†. / Saliba, Jason; Evensen, Nikki A.; Meyer, Julia A.; Newman, Daniel; Nersting, Jacob; Narang, Sonali; Ma, Xiaotu; Schmiegelow, Kjeld; Carroll, William L.
In: Pediatric Blood & Cancer, Vol. 67, No. 7, e28306, 07.2020.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Feasibility of monitoring peripheral blood to detect emerging clones in children with acute lymphoblastic leukemia†
AU - Saliba, Jason
AU - Evensen, Nikki A.
AU - Meyer, Julia A.
AU - Newman, Daniel
AU - Nersting, Jacob
AU - Narang, Sonali
AU - Ma, Xiaotu
AU - Schmiegelow, Kjeld
AU - Carroll, William L.
PY - 2020/7
Y1 - 2020/7
N2 - Relapse-enriched somatic variants drive drug resistance in childhood acute lymphoblastic leukemia. We used digital droplet-based polymerase chain reaction to establish whether relapse-enriched mutations in emerging subclones could be detected in peripheral blood samples before frank relapse. Although limitations in sensitivity for some probes hindered detection of certain variants, we successfully detected variants in NT5C2 and PRPS1 at a fractional abundance of 0.005% to 0.3%, 41 to 116 days before relapse. As mutations in both these genes confer resistance to thiopurines, early detection protocols using peripheral blood could be implemented to preemptively alter maintenance therapy to extinguish resistant clones before overt relapse.
AB - Relapse-enriched somatic variants drive drug resistance in childhood acute lymphoblastic leukemia. We used digital droplet-based polymerase chain reaction to establish whether relapse-enriched mutations in emerging subclones could be detected in peripheral blood samples before frank relapse. Although limitations in sensitivity for some probes hindered detection of certain variants, we successfully detected variants in NT5C2 and PRPS1 at a fractional abundance of 0.005% to 0.3%, 41 to 116 days before relapse. As mutations in both these genes confer resistance to thiopurines, early detection protocols using peripheral blood could be implemented to preemptively alter maintenance therapy to extinguish resistant clones before overt relapse.
KW - backtracking
KW - clonal evolution
KW - ddPCR
KW - relapsed acute lymphoblastic leukemia
KW - thiopurines
U2 - 10.1002/pbc.28306
DO - 10.1002/pbc.28306
M3 - Journal article
C2 - 32391957
AN - SCOPUS:85084420194
VL - 67
JO - Pediatric Blood & Cancer
JF - Pediatric Blood & Cancer
SN - 1545-5009
IS - 7
M1 - e28306
ER -
ID: 244204495