Current Ph-like ALL genetic testing algorithm used by the Children's Oncology Group. Diagnostic leukemia cells from children with high risk B-ALL are first screened for the Ph-like ALL gene expression signature using an 8-gene low density microarray (LDA) that includes CRLF2 as one of the 8 assessed genes.⁵¹  Specimens with the Ph-like ALL signature that lack BCR-ABL1 fusion (Ph⁺ ALL) undergo additional genetic testing. Those with high CRLF2 expression are assessed for P2RY8-CRLF2 and IGH-CRLF2 rearrangements by RT-PCR and FISH, respectively, and for JAK1, JAK2 and IL7R mutations by PCR. Ph-like ALL specimens without CRLF2 overexpression undergo multiplex RT-PCR fusion testing to detect ABL-class, JAK2, and EPOR rearrangements. Not all Ph-like fusions will be detected by this algorithm. Complete assessment may require alternative assays for identification, such as RNA-sequencing or unbiased fusion testing capable of identifying new 5′ partners. HR B-ALL, high-risk B-ALL.