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Clonal conversion of B-lymphoid leukemia reveals cross-lineage transfer of malignant states.

ABSTRACT: Even though leukemia is considered as confined to one specific hematopoietic cell type, cases of acute leukemia of ambiguous lineage and patients relapsing in phenotypically altered disease suggest that a malignant state may be transferred between lineages. Because B-cell leukemia is associated with mutations in transcription factors of importance for stable preservation of lineage identity we here investigated the potential lineage plasticity of leukemic cells. We report that primary pro-B leukemia cells from mice carrying heterozygous mutations in either of or both the Pax5 and Ebf1 gene, commonly mutated in human leukemia, can be converted into T-lineage leukemia cells. Even though the conversion process involved global changes in gene expression and lineage restricted epigenetic reconfiguration, the malignant phenotype of the cells was preserved enabling them to expand as T-lineage leukemia cells in vivo. Furthermore, while the transformed pro-B cells displayed plasticity towards myeloid lineages, the converted cells failed to cause myeloid leukemia after transplantation. These data provide evidence that a malignant phenotype can be transferred between hematopoietic lineages. This has important implications for modern cancer medicine because lineage targeted treatment of leukemia patients can be predicted to provoke the emergence of phenotypically altered sub-clones causing clinical relapse.

ORGANISM(S): Mus musculus

PROVIDER: GSE90655 | GEO | 2016/12/20

SECONDARY ACCESSION(S): PRJNA355290

REPOSITORIES: GEO

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