Which chromosomal translocation is associated with chronic myeloid leukemia (CML)?

Which chromosomal translocation is associated with chronic myeloid leukemia (CML)?

• A. t(9;22)
• B. t(8;21)
• C. t(11;14)
• D. t(14;18)

Answer: (A)

The translocation between chromosome 9 and chromosome 22 creates the Philadelphia chromosome, which fuses the BCR gene on 22 with the ABL1 gene on 9 to form the BCR-ABL fusion. This fusion produces a constitutively active tyrosine kinase that drives uncontrolled proliferation of myeloid cells, a hallmark of chronic myeloid leukemia. That specific genetic change is the defining association for CML, and it explains why targeted drugs that inhibit the BCR-ABL kinase are effective in treatment. In contrast, the other translocations listed are linked to different cancers (for example, RUNX1-RUNX1T1 in a subset of AML, CCND1-IGH in mantle cell lymphoma, and BCL2-IGH in follicular lymphoma), not CML.

The translocation between chromosome 9 and chromosome 22 creates the Philadelphia chromosome, which fuses the BCR gene on 22 with the ABL1 gene on 9 to form the BCR-ABL fusion. This fusion produces a constitutively active tyrosine kinase that drives uncontrolled proliferation of myeloid cells, a hallmark of chronic myeloid leukemia. That specific genetic change is the defining association for CML, and it explains why targeted drugs that inhibit the BCR-ABL kinase are effective in treatment. In contrast, the other translocations listed are linked to different cancers (for example, RUNX1-RUNX1T1 in a subset of AML, CCND1-IGH in mantle cell lymphoma, and BCL2-IGH in follicular lymphoma), not CML.