ETV6-ABL1-positive "chronic myeloid leukemia": clinical and molecular response to tyrosine kinase inhibition
Year: 2010
Type: article
Abstract: ETV6-ABL1-positive "chronic myeloid leukemia": clinical and molecular response to tyrosine kinase inhibitionWhile great progress has been achieved in the clinical management and molecular understanding of Ph+ chronic myeloid leukemia (CML), little is known about the optimal approach to monitor and treat patients with ETV6-ABL1 + myeloproliferative neoplasms.2][3][4][5][6][7][8][9] The ETV6-ABL1 fusion gene has also been identified in 3 patients with chronic myeloproliferative neoplasms other than "chronic myeloid leukemia" (cMPN) as well as 7 patients with BCR-ABL1 negative acute lymphoblastic leukemia and 4 patients with acute myeloid leukemia. 10,11 f the 9 cases of ETV6-ABL1 + chronic myeloid leukemia, only 2 were treated with a TKI in chronic phase 4, 5 and only one of these reached a complete remission with a modest follow up of seven months (no molecular monitoring was performed). 4 Among the other published ETV6-ABL1 + reports, one patient was treated with a second generation TKI for a relapsed cMPN. 12We provide the first molecular documentation of sustained remission of ETV6-ABL1 + chronic phase "chronic myeloid leukemia" (CML requires a BCR-ABL1 fusion according to the most recent 2008 WHO classification) to TKI.Molecular monitoring for the ETV6-ABL1 transcript is important given the fact that conventional karyotyping frequently fails to detect a cryptic translocation, i.e. the t(9;12).We provide evidence that treatment of ETV6-ABL1+ "chronic myeloid leukemia" with imatinib results in downregulation of C-MYC, BCL-XL, ID1 and NUP98, mediators of BCR-ABL1 transforming activity.Moreover, we found no associated mutations in UTX, ASXL1, EZH2, TET2 and IDH1/2 suggesting that ETV6-ABL1 + "chronic myeloid leukemia" may be as tyrosine kinase focused as BCR-ABL1 driven disease.The patient is a 36-year male who was found to have splenomegaly and a total white blood cell (WBC) count
Source: Haematologica
Institutions: Memorial Sloan Kettering Cancer Center, Kyoto University
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,157
OpenAlex ID: W2104647405