American Society of Hematology

Figure 1

$Spliceosome mutations and coexisting oncogenic mutations in children with MDS and JMML. (A) Mutations identified in 3 children. (B) Clinical timeline of patient D361. After second HSCT, the patient did not reach complete remission. Direct sequencing identified an SRSF2 mutation that was present only at diagnosis but was undetectable at later time points. A mutation in NRAS exon 1 (p.G13D) was detectable at all time points. In contrast, the mutation in NRAS exon 2 (p.Q61K) was present only at time of disease progression after second HSCT. This was confirmed by denaturing high-performance liquid chromatography. Bold lines represent patients' samples; and dashed lines, a wild-type control DNA. The picture at the bottom illustrates the hypothetical clonal evolution; black circles represent a clone carrying both the NRAS(p.G13D) and the SRSF2 mutation; gray circles, a primary clone harboring only the NRAS(p.G13D) mutation; and striped circles, a secondary clone with double NRAS mutation (p.G13D and p.Q61K). (C) Clinical timeline of patient D717. Mixed chimerism with 35% autologous cells occurred at 24 months after HSCT. Results from direct sequencing are presented within dashed boxes. The results from allele-specific clonal sequencing are shown at the bottom; the filled bars represent the proportion of mutant U2AF35 and KIT alleles. Twenty-three U2AF35 and 25 KIT subcloned alleles were sequenced in the diagnostic sample, and 25 U2AF35 and 31 KIT subcloned alleles were sequenced in the post-HSCT sample. SM-AHNMD indicates systemic mastocytosis associated with a clonal hematologic nonmast cell lineage disease; RCC, refractory cytopenia of childhood; CR, complete remission; DHPLC, denaturing high-performance liquid chromatography; MRD, matched related donor; MUD, matched unrelated donor; MC, mixed chimerism; and WT, wild-type.$

Spliceosome mutations and coexisting oncogenic mutations in children with MDS and JMML. (A) Mutations identified in 3 children. (B) Clinical timeline of patient D361. After second HSCT, the patient did not reach complete remission. Direct sequencing identified an SRSF2 mutation that was present only at diagnosis but was undetectable at later time points. A mutation in NRAS exon 1 (p.G13D) was detectable at all time points. In contrast, the mutation in NRAS exon 2 (p.Q61K) was present only at time of disease progression after second HSCT. This was confirmed by denaturing high-performance liquid chromatography. Bold lines represent patients' samples; and dashed lines, a wild-type control DNA. The picture at the bottom illustrates the hypothetical clonal evolution; black circles represent a clone carrying both the NRAS(p.G13D) and the SRSF2 mutation; gray circles, a primary clone harboring only the NRAS(p.G13D) mutation; and striped circles, a secondary clone with double NRAS mutation (p.G13D and p.Q61K). (C) Clinical timeline of patient D717. Mixed chimerism with 35% autologous cells occurred at 24 months after HSCT. Results from direct sequencing are presented within dashed boxes. The results from allele-specific clonal sequencing are shown at the bottom; the filled bars represent the proportion of mutant U2AF35 and KIT alleles. Twenty-three U2AF35 and 25 KIT subcloned alleles were sequenced in the diagnostic sample, and 25 U2AF35 and 31 KIT subcloned alleles were sequenced in the post-HSCT sample. SM-AHNMD indicates systemic mastocytosis associated with a clonal hematologic nonmast cell lineage disease; RCC, refractory cytopenia of childhood; CR, complete remission; DHPLC, denaturing high-performance liquid chromatography; MRD, matched related donor; MUD, matched unrelated donor; MC, mixed chimerism; and WT, wild-type.

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