Related Experiment Videos
Is the chromosomal region 9q34 always involved in variants of the Ph1 translocation?
Insights
Six variants of the Philadelphia chromosome (Ph1) translocation, often linked to chronic myeloid leukemia (CML), were analyzed. Most Ph1 variants are complex translocations involving chromosome 9q34, crucial for CML development.
Area of Science:
- Cytogenetics
- Hematology
- Oncology
Background:
- The Philadelphia chromosome (Ph1) is a hallmark of chronic myeloid leukemia (CML).
- Understanding Ph1 translocation variants is key to elucidating CML pathogenesis.
Purpose of the Study:
- To characterize six variants of the Ph1 translocation.
- To investigate the genetic mechanisms underlying Ph1-positive leukemias.
Main Methods:
- G-banding, Q-banding, and high-resolution R-banding.
- In situ hybridization techniques.
Main Results:
- Five cases presented with CML, and one with acute lymphocytic leukemia (ALL).
- Three variants were complex translocations involving chromosomes #9, #22, and a third chromosome.
- High-resolution banding and in situ hybridization confirmed involvement of 9q34 in all variants, suggesting they are complex translocations.
Conclusions:
- Most, if not all, Ph1 variants are complex translocations.
- The specific interaction between 22q11 and 9q34 (carrying c-abl) is essential for Ph1-positive CML development.
Abstract:
Six variants of the Ph1 translocation are described. The clinical diagnoses were chronic myeloid leukemia (CML) in 5 cases (patients 1-5) and acute lymphocytic leukemia (ALL) in patient 6. Three Ph1 variants were clear complex translocations, involving chromosomes #9, #22, and a third chromosome, i.e., #16, #11, or #14. The other three Ph1 variants appeared as "simple" translocations between chromosome #22 and chromosome #19, #4, or #12 when G- or Q-banding were used. When studied with high resolution R-banding, a small deletion of the terminal part of one chromosome #9 was visible, strongly suggesting that these variants were also complex translocations, i.e., t(9;19;22)(q34;p13;q11),t(4;9;22) (p16;q34;q11), and t(9;12;22)(q34;p13;q11). In the latter two cases, using in situ hybridization techniques, we demonstrated the presence of c-abl sequences on the Ph1 chromosome. This proved the involvement of 9q34 in these two variants. Our proposal is that most, and probably all, variants of Ph1 are complex translocations involving part of 9q34 and that the conjunction of a specific region of 22q11 with a specific segment of 9q34 (carrying the c-abl protooncogene) is essential for the development of Ph1 + CML.