ALDH1L2

Overview

ALDH1L2 (Aldehyde Dehydrogenase 1 Family Member L2) encodes a mitochondrial aldehyde dehydrogenase involved in the folate/one-carbon metabolic pathway. In melanoma, ALDH1L2 expression is associated with mesenchymal/invasive transcriptional programs that correlate with innate resistance to anti-PD-1 immunotherapy.

Alterations observed in the corpus

• Expression associated with the IPRES (innate anti-PD-1 resistance) transcriptional signature in pretreatment metastatic melanoma tumors; upregulated in non-responding tumors as part of a wound-healing/ECM/mesenchymal program PMID:26997480

Cancer types (linked)

• SKCM (melanoma): ALDH1L2 expression linked to the IPRES innate anti-PD-1 resistance program; elevated in pretreatment non-responding tumors PMID:26997480

Co-occurrence and mutual exclusivity

• Co-enriched with other IPRES genes including AXL, ROR2, WNT5A, LOXL2, TWIST2 in non-responding melanoma PMID:26997480

Therapeutic relevance

• ALDH1L2 expression as a component of IPRES may be relevant to stratification of patients for anti-PD-1 therapy; no direct therapeutic agent targets this gene PMID:26997480

Open questions

• Whether pharmacological suppression of the IPRES program (including ALDH1L2) restores anti-PD-1 sensitivity is unresolved and identified as a next step PMID:26997480

Sources

• PMID:26997480

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