Supplementary Figures 1-19 from Acute Lymphoblastic Leukemia with Myeloid Mutations Is a High-Risk Disease Associated with Clonal Hematopoiesis
Authors: Saygin Caner , Zhang Pu , Stauber Jacob , Aldoss Ibrahim , Sperling Adam S. , Weeks Lachelle D. , Luskin Marlise R. , Knepper Todd C. , Wanjari Pankhuri , Wang Peng , Lager Angela M. , Fitzpatrick Carrie , Segal Jeremy P. , Gharghabi Mehdi , Gurbuxani Sandeep , Venkataraman Girish , Cheng Jason X. , Eisfelder Bart J. , Bohorquez Oliver , Patel Anand A. , Umesh Nagalakshmi Sheethal , Jayaram Savita , Odenike Olatoyosi M. , Larson Richard A. , Godley Lucy A. , Arber Daniel A. , Gibson Christopher J. , Munshi Nikhil C. , Marcucci Guido , Ebert Benjamin L. , Greally John M. , Steidl Ulrich , Lapalombella Rosa , Shah Bijal D. , Stock Wendy 
Published: May 2024

<p>Supplemental Figure 1. WHO/ICC subtypes for the B-ALL cohort.</p><p>Supplemental Figure 2. Lymphoid clonal hematopoiesis (CH) mutations are less common in adults with ALL.</p><p>Supplemental Figure 3. Blast percentage in the pre-treatment sample and detected variant allelic frequencies (VAF) of mutations in ALL patients with myeloid mutations.</p><p>Supplemental Figure 4. Germline testing in the adult ALL cohort.</p><p>Supplemental Figure 5. Associations of gene mutations and WHO/ICC disease subtypes in B-ALL.</p><p>Supplemental Figure 6. Overall survival in adults with B-ALL.</p><p>Supplemental Figure 7. Kaplan-Meier overall survival curves for Ph-negative B-ALL patients stratified based on the presence of TP53 and non-TP53 MyM (A), and treatment with different chemotherapy protocols (B, C, D). LH, low hypodiploidy.</p><p>Supplemental Figure 8. T-lineage ALL with myeloid mutations (MyM).</p><p>Supplemental Figure 9. Expression levels of lineage-specific surface markers.</p><p>Supplemental Figure 10. Single cell DNA and protein sequencing to study the clonal architecture of Tlineage ALL with MyM.</p><p>Supplemental Figure 11. A, Flow plots showing ETP-lymphoblast, myeloid, and mature lymphocytic compartments of ETP-ALL1, which were sorted for DNA extraction and sequencing. B, Distribution of variant allelic frequencies (VAFs) for myeloid (IDH2, DNMT3A) and NRAS mutations across subpopulations of cells in ETP-ALL1.</p><p>Supplemental Figure 12. Clonal dynamics of ALL with MyM.</p><p>Supplemental Figure 13. Two CH mutations (TP53 and DNMT3A) were detectable seven years before the diagnosis of therapy-related ALL22.</p><p>Supplemental Figure 14. Clonal evolution of B-ALL2.</p><p>Supplemental Figure 15. Lymphoblasts from B-ALL with MyM are characterized by their resistance to cytotoxic chemotherapy.</p><p>Supplemental Figure 16. Curves showing viability of primary human B-ALL samples with TP53 mutation (n= 14), MyM (n= 16) and no MyM/TP53 (n= 24), treated with vincristine, doxorubicin, and blinatumomab at escalating doses.</p><p>Supplemental Figure 17. Flow cytometry plots showing ALL22 (TP53-mutated B-ALL) sample treated with escalating doses of blinatumomab.</p><p>Supplemental Figure 18. A, CR with MRD negativity rates in Ph-negative B-ALL patients treated with pediatric regimens, stratified based on age, gender, and treatment site. B, CR with MRD negativity rates in Ph-negative B-ALL patients treated with hyper-CVAD, stratified based on age, gender, and treatment site. C, CR with MRD negativity rates in Ph-negative B-ALL patients treated with inotuzumab.</p><p>Supplemental Figure 19. A, MHC class I and II antigen expression in blasts from B-ALL with MyM vs B-ALL without MyM/TP53. B, Comparison of genes implicated in blinatumomab resistance in B-ALL with vs without MyM/TP53.</p>