72. Variant curation of BCR::ABL1-like B-lymphoblastic leukemia/lymphoma through expert panel consensus

Aly Abdelkareem

Mark Evans

Raised in Salt Lake City, Mark Evans received his Bachelor of Science degree from Stanford University and his Doctor of Medicine degree from the University of Utah School of Medicine. He completed the anatomic and clinical pathology residency program at the University of California, Irvine, followed by fellowship training in hematopathology at Brigham and Women’s Hospital and in molecular genetic pathology at MD Anderson Cancer Center. Mark is currently employed as an oncologic pathologist at Caris Life Sciences and teaches adjunctly at the University of Southern California. His research interests include breast implant-associated malignancies, B-lymphoblastic leukemia/lymphoma, and emerging next-generation sequencing technologies.


Mark G. Evansa, Jason Salibab, Yassmine Akkaric, Deepa Bhojwanid, Piers Blomburye, Arpad Danosb, Paul G. Eckertf, Mark D. Ewaltg, Sandeep Gurbuxanih, Christine J. Harrisoni, Ilaria Iacobuccij, Shai Izraelik, Nitin Jainl, Rashmi Kanagal-Shamannal, Chimène Kesserwanm, Alexandra E. Kovachd, Kristy Leen, Hannah Helbero, Valentina Nardip, Shalini Reshmiq, Kathryn Robert j, Alexandre Rouetter, Neerav Shuklag, Wendy Stockh, Panieh Terrafg, Xinjie Xus, Liying Zhangt, Xiaonan Zhaou, Yiming Zhongv, Gordana Racad, Obi L. Griffithb, Malachi Griffithb, Kilannin Krysiakb, Charles Mullighanj

aThe University of Texas MD Anderson Cancer Center, Houston, TX, USA; bWashington University School of Medicine, St. Louis, MO, USA; cLegacy Health, Portland, OR, USA; dChildren’s Hospital Los Angeles, Los Angeles, CA, USA; ePeter MacCallum Cancer Centre, Melbourne, VIC, AU; fChildren’s Cancer Institute, Peter MacCallum Cancer Centre, Melbourne, VIC, AU; gMemorial Sloan Kettering Cancer Center, New York, NY, USA; hUniversity of Chicago, Chicago, IL, USA; iNewcastle University Centre for Cancer, Newcastle upon Tyne, TWR, UK; jSt. Jude Children’s Research Hospital, Memphis, TN, USA; kSchneider Children’s Medical Center of Israel, Tel Aviv, IL; lThe University of Texas MD Anderson Cancer Center, Houston, TX, USA; mNational Cancer Institute, Bethesda, MA, USA; nSema4, Stamford, CT, USA; oBaylor College of Medicine/Texas Children’s Hospital, Houston, TX, USA; pMassachusetts General Hospital, Boston, MA, USA; qNationwide Children’s Hospital, Columbus, OH, USA; rSainte-Justine Hospital, Montreal, QC, CA; sMayo Clinic, Rochester, MN, USA; tUniversity of California at Los Angeles, Los Angeles, CA, USA; uBaylor College of Medicine, Houston, TX, USA; vChildren’s Hospital of Philadelphia, Philadelphia, PA, USA

BCR::ABL1-like B-lymphoblastic leukemia/lymphoma (B-ALL) is a neoplasm of precursor B cells and a subtype of high-risk B-ALL that exhibits a gene expression profile similar to that of BCR::ABL1-positive B-ALL while lacking the BCR::ABL1 fusion protein. Instead, it is characterized by somatic variants in a variety of cytokine receptor and kinase encoding genes. This genetic heterogeneity poses challenges for accurate and comprehensive laboratory diagnosis and clinical decision making including prognostication and therapeutic interventions.

To create a consensus for curation and variant classification related to this disease subtype, a panel of experts was assembled, forming a ClinGen Somatic Cancer Variant Curation Expert Panel (SC-VCEP). The membership of this panel represents a collaboration between the ClinGen Somatic Pediatric Cancer and Somatic Hematological Cancer Taskforces, and includes internationally-recognized experts in the field of BCR::ABL1-like B-ALL. The expert panel was surveyed to identify high-priority variants for discussion, with an emphasis on kinase signaling activating mutations and genomic aberrations associated with BCR::ABL1-like B-ALL.

Members will undertake evidence-based curation of variants in the Clinical Interpretation of Variants in Cancer knowledgebase (CIViC; civicdb.org). Upon the conclusion of its efforts, the expert panel will have created specifications to AMP/ASCO/CAP guidelines [PMID: 27993330] for genetic alterations relevant to BCR::ABL1-like B-ALL, interpreted variants according to these rules, and made finalized interpretations publicly available through CIViC and ClinVar (ncbi.nlm.nih.gov/clinvar/). The ultimate goal is to establish an ongoing consensus interpretation of genetic changes with diagnostic, prognostic, and therapeutic implications in BCR::ABL1-like B-ALL.