1. Invariant phenotype and molecular association of biallelic TET2 mutant myeloid neoplasia
by Hassan Awada, Yasunobu Nagata, Abhinav Goyal, Mohammad F. Asad, Bhumika Patel, Cassandra M. Hirsch, Teodora Kuzmanovic, Yihong Guan, Bartlomiej P. Przychodzen, Mai Aly, Vera Adema, Wenyi Shen, Louis Williams, Aziz Nazha, Mohamed E. Abazeed, Mikkael A. Sekeres, Tomas Radivoyevitch, Torsten Haferlach, Babal K. Jha, Valeria Visconte, and Jaroslaw P. Maciejewski
BloodAdv
Volume 3(3):
February 12, 2019
© 2019 by The American Society of Hematology

2. Hassan Awada et al. Blood Adv 2019;3:339-349
© 2019 by The American Society of Hematology

3. TET2 gene mutation classification, type, and clinical characteristics.
TET2 gene mutation classification, type, and clinical characteristics. (A) Scatterplot of the VAFs of patients with TET2MT. The VAF of first-hit TET2MT was plotted on the x-axis and that of the second-hit TET2MT, if present, on the y-axis. Patients were categorized into 5 groups as explained in the text. The red oval corresponds to biTET2MT cases, the gray bar to undetermined cases, the blue oval to biclonal TET2MT cases, the light green oval to monoTET2MT cases, and the yellow oval to hemihomozygous TET2MT (UPD) cases. (B) Percentages of different types of TET2MT in biTET2i cases and significance of truncating mutations vs monoTET2MT. Fisher’s exact test was used for analysis. (C) Bar graphs showing the distribution of biTET2i and monoTET2MT cases per diagnosis and cytogenetics. The bar columns indicate percentages. (D) Pie chart showing the percentage of cases per configuration. (E) Pie charts of biTET2i, monoTET2MT, and TET2WT respectively representing the percentage of cases per classification. CMML (+) indicates cases with CMML at the time of presentation, CMML (−) indicates no CMML diagnosis, monocytosis (+) indicates the presence of monocytosis, and monocytosis (−) indicates the absence of monocytosis.
Hassan Awada et al. Blood Adv 2019;3:
© 2019 by The American Society of Hematology

4. Clonal architecture and hierarchy of TET2MT in biTET2i.
Clonal architecture and hierarchy of TET2MTin biTET2i. (A) Plot showing dominant, codominant, and secondary mutations in the 82 biTET2i patients. Mutated gene names, cytogenetics, and diagnosis are color coded as indicated. For this presentation, only genes mutated ≥3 times among the biTET2i population are represented. Each column represents 1 patient, and each row corresponds to 1 gene or family of genes. (B) Pie chart displaying the percentage of first-hit TET2 occurring as dominant (ancestral), codominant (ancestral), and subclonal (secondary) in the biTET2i population. (C-E) The bar graphs show the percentages of the corresponding dominant genes to the secondary/subclonal first-hit TET2 gene (C), secondary clones to the dominant first-hit TET2 gene (D), and codominant genes to the codominant first-hit TET2 gene (E). (F) Frequency (in percentage) of mutations in selected genes in the population. Ten genes that are frequently mutated in myeloid neoplasms were selected. Columns are color coded per TET2MT configuration (TET2WT, monoTET2MT, and biTET2i).
Hassan Awada et al. Blood Adv 2019;3:
© 2019 by The American Society of Hematology

5. Significance of concurrent gene mutations in biTET2i and correlation per disease subtype.
Significance of concurrent gene mutations in biTET2iand correlation per disease subtype. (A) Forest plot showing the OR of associated gene mutations in biTET2i vs biTET2− cases. As indicated, red squares correspond to significant cases, while red stars correspond to highly significant cases. Fisher’s exact test was used to test significance. (B) Frequency (in percentage) of mutations in selected genes per disease subtype in biTET2i vs biTET2−. Significance was tested via Fisher’s exact test.
Hassan Awada et al. Blood Adv 2019;3:
© 2019 by The American Society of Hematology

6. Univariate analysis for baseline, clinical, and genomic features in biTET2i vs wild-type.
Univariate analysis for baseline, clinical, and genomic features in biTET2ivs wild-type. Univariate analysis showing the significant results for baseline (older age, lower risk, MDS, MDS/MPN, CMML, and normal cytogenetics), clinical (leukopenia, neutropenia, monocytosis, pancytopenia, BM blasts, BM hypercellularity, and myeloid dysplasia), and genomic (KRAS/NRASMT, SRSF2MT, and TP53MT) features in biTET2i vs TET2WT.
Hassan Awada et al. Blood Adv 2019;3:
© 2019 by The American Society of Hematology