Advertisement

Clinicopathologic and genetic characterization of nonacute NPM1-mutated myeloid neoplasms

Sanjay S. Patel, Caleb Ho, Ryan N. Ptashkin, Sam Sadigh, Adam Bagg, Julia T. Geyer, Mina L. Xu, Thomas Prebet, Emily F. Mason, Adam C. Seegmiller, Elizabeth A. Morgan, David P. Steensma, Eric S. Winer, Waihay J. Wong, Robert P. Hasserjian and Olga K. Weinberg

Article Figures & Data

Figures

  • Figure 1.

    Genetic and clinical outcome characteristics of NPM1MN, NPM1+MN, and NPM1+AML. (A) Heatmap of commonly evaluated genes, cytogenetic findings, and total mutational counts across all cases of NPM1 MN (n = 95), NPM1+ MN (n = 45), and NPM1+ AML (n = 119). Each column represents an individual patient. All comutations (filled squares = mutation identified) and cytogenetic findings (filled squares = identified deviation from 46,XX or 46,XY) in binary format. Total mutation count per case stratified at greater than (filled square) or less than or equal to 2, by cohort as follows: NPM1 MN (46/95), NPM1+ MN (21/45), and NPM1+ AML (101/119). *Statistically significant differences in proportions between flanking groups (P < .05, Fisher’s exact test). (B) NPM1+ MN (n = 45) exhibit shorter median OS (20 months) than NPM1- MN (36.6 months, n = 95), and NPM1+ AML (42.4 months, n = 119).

Tables

  • Table 1.

    Characteristics of NPM1 MN, NPM1+ MN, and NPM1+ AML cohorts

    NPM1 MN (n = 95)NPM1+ MN (n = 45)NPM1+ AML (n = 119)
    Patient characteristics
     Median age (range), y68 (38-84)*63 (36-96)61 (15-85)
     Male:female1.91.00.75
    Clinical parameters
     Hemoglobin, median (range), g/dL9.7 (4.8-15.9)9.0 (6.1-12.7)9.0 (5.7-15)
     WBC, median (range), ×109/L3.5 (0.6-69.4)3.3 (1.2-225)21 (0.69-340)*
     Platelet count, median (range), ×109/L84 (15-808)79 (15-607)72 (10-356)
     Median of BM cellularity (range), %70 (10-95)80 (10-100)90 (30-98)*
     Median of BM blasts (range), %8 (1-18)10 (1-19)73 (21-96)*
    Diagnosis, n (%)
     MDS non-EB5 (5)2 (4)NA
     MDS-EB55 (58)24 (53)NA
     CMML16 (17)9 (20)NA
     MDS/MPN (non-CMML)8 (8)5 (11)NA
     t-MN11 (12)5 (11)NA
     AMLNANA119 (100)
    IPSS-R scores (MDS cases only), median (range)5.0 (1.0-10.0)5.0 (1.5-7.0)NA
    Outcome
     Median follow-up time (range), mo19.4 (0.3-57)10 (0.07-70)24 (0.13-125)
     Alive at last follow-up, n (%)53 (56)29 (64)67 (56)
     Progression to AML, n (%)30 (32)20 (44)NA
     Median time to progression (range), mo6.3 (1.7-43)5.2 (0.4-17.5)NA
    Received upfront HMA therapy, n (%)55 (58)33 (73)5 (4)
    Received upfront induction chemotherapy, n (%)0 (0)3 (7)113 (95)
    Received SCT at any time, n (%)44 (46)19 (42)67 (56)
    • BM, bone marrow; EB, excess blasts; NA, not available; t-MN, therapy-related myeloid neoplasm.

    • * P < .05 for difference in comparison with NPM1+ MN group (Mann-Whitney U test).

  • Table 2.

    Genetic features of NPM1 MN, NPM1+ MN, and NPM1+ AML cohorts

    NPM1 MN (n = 95)NPM1+ MN (n = 45)NPM1+ AML (n = 119)
    Comutations, by pathway, n (%)
     DNMT3A14 (15)*15 (33)57 (48)
     IDH122 (2)4 (9)*25 (21)*
     IDH25 (5)2 (4)*16 (13)*
     TET229 (31)7 (16)32 (27)
     ASXL130 (32)*4 (9)3 (3)
     RUNX120 (21)*0 (0)1 (0.8)
     KRAS3 (3)1 (2)4 (3)
     NRAS8 (8)4 (9)27 (23)
     FLT3 (non-ITD)1 (1)3 (7)29 (24)
     FLT3-ITD1 (1)1 (2)36 (30)
     PTPN112 (2)*6 (13)25 (21)
     SRSF220 (21)3 (8)9 (8)
     SF3B19 (9)4 (9)1 (0.8)
     TP5315 (16)*1 (2)0 (0)
    Mutation count, median (range)2 (0-8)2 (1-7)4 (1-8)§
    Abnormal karyotype, n (%)57 (61)*5 (12)18 (16)
    • * IDH1 and IDH2 are grouped for the analysis comparing NPM1+ MN with NPM1+ AML (Fisher's exact test).

    • KRAS and NRAS are grouped for the analysis comparing NPM1+ MN with NPM1+ AML (Fisher's exact test).

    • Significantly different compared with NPM1+ MN (Fisher's exact test).

    • § P < .05 for difference compared with NPM1+ MN (Mann-Whitney U test).