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Study Finds Complex BCR-ABL1 Signal Patterns Linked to Poorer Prognosis in CML

By: Celeste L. Dixon
Posted: Thursday, December 12, 2019

Further knowledge of ABL kinase mutations is a key to learning more about disease relapse and resistance in BCR-ABL1–positive chronic myeloid leukemia (CML) and acute leukemia. Although recognizing that monitoring the expression of the BCR-ABL1 fusion gene and identifying ABL kinase mutations have been shown to help predict disease relapse and drug resistance, a team including Zhanglin Zhang, MD, of the Nanchang University in Nanchang, China, and colleagues, set out to explore the less-investigated prognostic impact of BCR-ABL1 signal patterns detected by fluorescence in situ hybridization (FISH).

The researchers analyzed FISH-detected patterns in 243 patients with chronic phase CML, 17 patients with blast phase CML, and 52 patients with BCR-ABL1–positive acute lymphoblastic leukemia (ALL). “The patterns presented complexity and diversity,” wrote Dr. Zhang and colleagues in BMC Cancer, with 12 different signals observed in the cohort: 1R1G2F, 1R1G1F, 2R1G1F, 1R2G1F, 2R2G1F, 1R2G2F, 1R1G3F, 1G3F, 2G3F, 1G4F, 1R1G4F, and 1R4F. Complex (two or more types) BCR-ABL1 signal patterns were observed in 52.9% (n = 9) of those with blast phase CML, 30.8% (n = 16) of the patients with ALL, and 2.1% (n = 5) of those with chronic phase CML. Of note, “five clonal evolution patterns related to disease progression and relapse were observed, and patients with complex BCR-ABL1 signal patterns had a poorer overall survival time compared with those with single patterns (5 vs. 15 months; P = .006).”

Clearly, the frequency of additional cytogenic abnormalities in CML increases the probability of the disease moving from the chronic phase to the blast phase. The data showed complex BCR-ABL1 signal patterns to be associated with both leukemic clonal evolution and poorer prognosis in BCR-ABL1–positive leukemia.

“Monitoring BCR-ABL1 signal patterns might be an effective means to provide prognostic guidance and treatment choices for these patients,” the authors suggested.

Disclosure: The study authors reported no conflicts of interest.



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