Human pediatric B-cell acute lymphoblastic leukemias can be classified as B-1 or B-2-like based on a minimal transcriptional signature

Briana Fitch; Ritu Roy; Huimin Geng; Encarnacion Montecino-Rodriguez; Henrik Bengtsson; Coline Gaillard; Kamir Hiam; David Casero; Adam B Olshen; Kenneth Dorshkind; Scott C Kogan

doi:10.1016/j.exphem.2020.09.184

Human pediatric B-cell acute lymphoblastic leukemias can be classified as B-1 or B-2-like based on a minimal transcriptional signature

Exp Hematol. 2020 Oct:90:65-71.e1. doi: 10.1016/j.exphem.2020.09.184. Epub 2020 Sep 15.

Authors

Affiliations

¹ Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.
² Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA; Computational Biology and Informatics, University of California, San Francisco, San Francisco, CA.
³ Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA.
⁴ Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA.
⁵ Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA.
⁶ Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.
⁷ Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA; Computational Biology and Informatics, University of California, San Francisco, San Francisco, CA; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA.
⁸ Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA.
⁹ Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA. Electronic address: Scott.Kogan@ucsf.edu.

Abstract

The finding that transformed mouse B-1 and B-2 progenitors give rise to B-cell acute lymphoblastic leukemias (B-ALLs) with varied aggressiveness suggests that B-cell lineage might also be a factor in the initiation and progression of pediatric B-ALLs in humans. If this is the case, we hypothesized that human pediatric B-ALLs would share gene expression patterns with mouse B-1 or B-2 progenitors. We tested this premise by deriving a distinct 30-gene B-1 and B-2 progenitor signature that was applied to a microarray data set of human pediatric ALLs. Cluster analysis revealed that CRLF2, E2A-PBX1, ERG, and ETV6-RUNX1 leukemias were B-1-like, whereas BCR-ABL1, hyperdiploid, and MLL leukemias were B-2-like. Examination of the 30-gene signature in two independent data sets of pediatric ALLs supported this result. Our data suggest that common genetic subtypes of human ALL have their origin in the B-1 or B-2 lineage.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Child
Gene Expression Profiling*
Gene Expression Regulation, Leukemic*
Humans
Mice
Neoplasm Proteins* / biosynthesis
Neoplasm Proteins* / genetics
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma* / classification
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma* / genetics
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma* / metabolism
Transcriptome*

Substances

Neoplasm Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding