FP-003: BCR/ABL gene fusion detection kit

BCR/ABL1 Gene Fusion: Overview

The BCR/ABL1 fusion gene (historically called BCR-ABL) is the defining molecular hallmark of Chronic Myeloid Leukemia (CML) and a subset of Acute Lymphoblastic Leukemia (ALL). Its discovery revolutionized cancer biology and therapy, introducing the first successful targeted therapy for cancer.

Molecular Basis & Formation

Aspect	Description
Genetic Event	Reciprocal translocation between chromosomes 9 and 22: t(9;22)(q34;q11)
Resulting Chromosome	Creates the Philadelphia Chromosome (Ph+), a shortened chromosome 22.
Fusion Gene	5' BCR (Breakpoint Cluster Region, chr22) + *3' ABL1* (Abelson tyrosine kinase, chr9)
Key Consequence	Production of a constitutively active tyrosine kinase that drives leukemogenesis.

Clinical Significance & Therapeutic Paradigm

1. Diagnostic

• CML: Presence of BCR/ABL1 is pathognomonic. Diagnosis requires its detection.

• Ph+ ALL: Poor prognosis subgroup requiring specific therapy.

2. Monitoring Response to Therapy

• The quantitative measurement of BCR/ABL1 transcript levels is the cornerstone of CML management.

• Key Milestones (International Scale - IS):

  • Early Molecular Response (EMR): ≤10% BCR/ABL1 at 3 months.

  • Major Molecular Response (MMR): ≤0.1% BCR/ABL1 (MR³).

  • Deep Molecular Response (DMR): MR⁴ (≤0.01%) or MR⁴.⁵ (≤0.0032%).

• DMR is a prerequisite for attempting Treatment-Free Remission (TFR).

3. Guiding Therapy

• Tyrosine Kinase Inhibitors (TKIs) directly target the BCR/ABL1 protein.

  • 1st Gen: Imatinib (revolutionized CML treatment).

  • 2nd Gen: Dasatinib, Nilotinib, Bosutinib (more potent, for resistance/intolerance).

  • 3rd Gen: Ponatinib (active against T315I "gatekeeper" mutation).

4. Detecting Resistance

• Rising transcript levels indicate treatment failure.

• ABL1 Kinase Domain Mutation Analysis (via sequencing) identifies specific mutations (e.g., T315I) guiding TKI selection.

Key Takeaway

The BCR/ABL1 fusion gene is a disease-defining driver oncogene and a continuous biomarker for diagnosis, monitoring, and treatment guidance in CML and Ph+ ALL. Its management via quantitative PCR and TKIs represents one of the greatest success stories in modern medicine, transforming a fatal leukemia into a manageable chronic condition for most patients. The focus has shifted from survival to optimizing quality of life and achieving treatment-free remission.

[Instructions Manual] BCR/ABL gene fusion detection kit