EGFR, ABL and BCL2 genes and their roles in tumor development

1. Overview

These three genes illustrate the two main oncogenic themes: oncogene activation (EGFR, ABL) driving proliferation, and apoptosis evasion (BCL2).

2. EGFR (HER1/ErbB1) — receptor tyrosine kinase

• Normally: EGF binds → dimerization → autophosphorylation → active receptor → RAS/MAPK + PI3K/AKT → transcription, proliferation, survival. No ligand = no signal.
• Oncogenic activation — activating mutations (continuous signaling without ligand) or overexpression/amplification (hypersensitive even to trace ligand).
• Disease: squamous cell / adenocarcinoma of lung, others.
• Therapy — block the receptor: extracellular antibodies; small-molecule TK inhibitors (gefitinib/erlotinib).

3. ABL — non-receptor (cytoplasmic) tyrosine kinase

• Normally nuclear; regulates differentiation, division, adhesion, and promotes apoptosis in damaged cells.
• t(9;22) (Philadelphia chromosome): ABL (chr 9) fuses to BCR (chr 22) → BCR-ABL fusion protein → constitutive cytoplasmic TK → activates JAK-STAT, SRC, RAS → proliferation + impaired apoptosis.
• Disease: CML (~95%), also Ph+ ALL, rarely AML.
• Therapy — BCR-ABL inhibitors (imatinib).

4. BCL2 — anti-apoptotic mitochondrial protein

• Normally inhibits Bax/Bak → prevents mitochondrial cytochrome-c release → blocks intrinsic apoptosis.
• t(14;18): BCL2 (chr 18) placed under the IgH promoter (chr 14) → overexpression → B cells resist apoptosis → accumulate → follicular lymphoma (lymphadenopathy, marrow infiltration).

💡 High-yield: EGFR = RTK → RAS/MAPK + PI3K; activating mutation/amplification in lung cancer (anti-EGFR therapy). ABL = cytoplasmic TK; t(9;22) BCR-ABL = CML (imatinib). BCL2 = anti-apoptotic; t(14;18) overexpression = follicular lymphoma. Activation (EGFR/ABL) vs apoptosis evasion (BCL2).