Table of Contents
Definition / general | Essential features | Terminology | Pathophysiology | Clinical features | Microscopic (histologic) images | Positive staining - normal | Positive staining - disease | Negative stainsCite this page: Chan A, Enwere E. MYB. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsmyb.html. Accessed November 27th, 2024.
Definition / general
- A proto-oncogene
- The canonical member of the MYB family of transcription factor proteins
- Important regulator of hematopoiesis
- Significant contributing factor to induction of leukemia in humans (Leukemia 2013;27:269)
Essential features
- Essential for hematopoiesis and lymphoid development
- Expressed in nuclei of proliferating epithelial, endothelial and hematopoietic progenitor cells (erythroid, myeloid, lymphoid); as these mature and differentiate, MYB transcription levels decrease dramatically (Mol Biol Evol 2008;25:2189)
- Has hundreds of transcriptional targets, including genes involved in development, cell survival, proliferation and homeostasis (Nat Rev Cancer 2008;8:523)
- Oncogenic mutations in MYB alter the spectrum of its transcriptional targets
Terminology
- Also referred to as C - Myb, Cmyb, V - Myb avian myeloblastosis viral oncogene homolog, Efg
Pathophysiology
- MYB family proteins have three domains:
- Highly conserved N terminal DNA binding domain, which specifically recognizes the consensus sequence 5’-YAAC[GT]G-3’, where Y is any pYrimidine
- Transcriptional activation domain
- A less conserved C terminal domain mostly involved in transcriptional silencing
- Contains a leucine zipper - like motif that regulates MYB activity
- Disruption enhances the protein activity (Genes Dev 1996;10:1858)
- MYB knockout mice die in utero from severe anemia resulting from impaired hepatic hematopoiesis (Cell 1991;65:677)
- One study showed only 10 – 15% expression of MYB is required to allow 60% survival of mice for several months (EMBO J 2003;22:4478)
Clinical features
- Overexpression in many leukemias
- Increased MYB protein expression and MYB oncogene copy number observed in T cell acute lymphoblastic leukemia (Nat Genet 2007;39:593)
- Overexpression predicts poorer survival (Clin Cancer Res 2011;17:7003)
- Chromosomal translocation of MYB and NFIB creates a MYB - NFIB fusion gene in 50% of adenoid cystic carcinoma (ACC), resulting in active transcription of MYB target genes (Mod Pathol 2011;24:1169, Head Neck Pathol 2013;7:17 and Proc Natl Acad Sci U S A 2009;106:18740)
- MYB - NFIB fusion may be a diagnostic biomarker and therapeutic target for ACC; MYB overexpression is detected in up to 80% (Nat Genet 2013;45:791 and Clin Cancer Res 2010;16:4722)
- Mutations in the first intron of MYB disrupt expression of the gene; common in colorectal cancers (Genes Chromosomes Cancer 2006;45:1143)
Positive staining - normal
- Colon, rectum, hematopoietic stem cells
Positive staining - disease
- Adenoid cystic carcinoma
- Pancreatic, colon and breast cancer
- Leukemia and lymphoma
Negative stains
- Adipose tissue and skin