Oncogene–translocation–disease associations.
This is ideal for quick review or exams:
| Translocation / Fusion | Oncogene / Gene involved | Chromosomes | Disease / Cancer | Clinical Notes / Relevance |
|---|---|---|---|---|
| t(9;22) → BCR–ABL1 | ABL1 (tyrosine kinase) | 9q34; 22q11 | CML, Ph+ ALL | Constitutive tyrosine kinase → targeted by TKIs (imatinib, dasatinib). Diagnostic & monitoring marker. |
| t(8;14) → MYC–IgH | MYC | 8q24; 14q32 | Burkitt lymphoma | IgH enhancer → MYC overexpression → rapid proliferation. Diagnostic & prognostic; drives intensive chemo. |
| t(15;17) → PML–RARA | PML, RARA | 15q24; 17q21 | Acute promyelocytic leukemia (APL) | Blocks differentiation of promyelocytes. Targeted by ATRA + arsenic trioxide. |
| t(11;14) → CCND1–IgH | Cyclin D1 (CCND1) | 11q13; 14q32 | Mantle cell lymphoma | Overexpression of cyclin D1 → cell cycle dysregulation. Prognostic & diagnostic marker. |
| t(14;18) → BCL2–IgH | BCL2 | 14q32; 18q21 | Follicular lymphoma | Anti-apoptotic BCL2 overexpression → survival advantage. Guides prognosis; indirect treatment decisions. |
| t(2;5) → NPM–ALK | ALK (tyrosine kinase) | 2p23; 5q35 | Anaplastic large cell lymphoma (ALK+) | Constitutive kinase activity → targetable by ALK inhibitors (crizotinib). |
Tips for oncology pharmacy exams / practice:
- Translocation = Diagnostic + Therapeutic marker.
- MYC, BCL2, CCND1 → mainly proliferation/survival regulators (undruggable directly, but affect chemo intensity).
- Kinase fusions (BCR–ABL, NPM–ALK) → targetable with TKIs.
- PML–RARA → unique case where differentiation therapy is possible (ATRA/arsenic).
Concise “fusion gene → disease → targeted therapy”
| Fusion Gene / Translocation | Disease / Cancer | Pathophysiology / Key Effect | Targeted Therapy / Clinical Relevance |
|---|---|---|---|
| BCR–ABL1 (t9;22) | CML, Ph+ ALL | Constitutive ABL1 tyrosine kinase → uncontrolled proliferation | TKIs: imatinib, dasatinib, nilotinib, ponatinib; used for treatment and MRD monitoring |
| PML–RARA (t15;17) | Acute promyelocytic leukemia (APL) | Blocks differentiation of promyelocytes | ATRA + arsenic trioxide; differentiation therapy; rapid treatment critical to prevent DIC |
| MYC–IgH (t8;14) | Burkitt lymphoma | IgH enhancer → MYC overexpression → rapid proliferation | Intensive multi-agent chemo; MYC is undruggable directly; prognostic marker |
| CCND1–IgH (t11;14) | Mantle cell lymphoma | Cyclin D1 overexpression → cell cycle dysregulation | Guides prognosis and treatment planning; chemo ± targeted agents (BTK inhibitors) |
| BCL2–IgH (t14;18) | Follicular lymphoma | Anti-apoptotic BCL2 overexpression → cell survival | Indirect therapy implication; sometimes treated with BCL2 inhibitors (venetoclax) in relapsed cases |
| NPM–ALK (t2;5) | Anaplastic large cell lymphoma (ALK+) | Constitutive ALK kinase activity → uncontrolled proliferation | ALK inhibitors: crizotinib; targeted therapy for relapsed/refractory cases |
Tips for pharmacy exam / practice:
- Kinase fusions (BCR–ABL1, NPM–ALK) → directly targetable with TKIs or ALK inhibitors.
- Transcription factor fusions (MYC–IgH, PML–RARA) → may require chemotherapy or differentiation therapy.
- Apoptosis/cell cycle fusions (BCL2–IgH, CCND1–IgH) → mainly prognostic, guide therapy intensity or use of pathway-specific inhibitors.
- Remember: Translocation = Diagnostic + Prognostic + Sometimes Therapeutic marker.