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A recent study identified a mutation in LLGL2 (HGNC:6629) in a sub‐clone of hematopoietic cells during the progression from severe congenital neutropenia to acute myeloid leukemia (MONDO_0018874) in a single patient PMID:22371884. Although multiple acquired mutations were reported, the presence of a LLGL2 alteration suggests that disruption of cell polarity regulators may contribute to leukemic transformation. The genetic evidence remains limited due to its identification in only one proband without extensive segregation data.
Functional assessment of LLGL2 has further supported its potential role in tumorigenesis. A study characterizing the promoter of Hugl-2, the human homologue of Drosophila lgl, demonstrated that transcriptional regulation by factors such as Sp-1 and EGF signaling could impact cell polarity and tumor suppression PMID:18155665. Although the functional data are promising, additional studies will be necessary to confirm the clinical utility of LLGL2 alterations in acute myeloid leukemia.
Gene–Disease AssociationLimitedLLGL2 mutation observed in a single SCN patient progressing to AML limits the overall support for the association PMID:22371884. Genetic EvidenceLimitedThe mutation was identified in one proband among several acquired variants, with insufficient segregation data to establish a stronger link PMID:22371884. Functional EvidenceModeratePromoter studies for Hugl-2 indicate that alterations in transcriptional regulation may contribute to loss of cell polarity and tumorigenesis, supporting a potential role in leukemic transformation PMID:18155665. |