Chronic myelocytic leukemia with eosinophilia, t(9;12)(q34;p13), and ETV6-ABL gene rearrangement

Keung, Yi‐Kong; Beaty, Michael W.; Steward, William P.; Jackle, Bethy; Pettnati, Mark

doi:10.1016/s0165-4608(02)00609-x

Cited by 55 publications

(32 citation statements)

References 27 publications

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“…1,18,[21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] Standard diagnostics, including molecular genetics, karyotyping and fluorescence in-situ hybridization (FISH) were performed according to the standard practice of the local diagnostic laboratories. Basic clinical/outcome data were collected from treating centers.…”

Section: Patientsmentioning

confidence: 99%

Characterization of leukemias with ETV6-ABL1 fusion

et al. 2016

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T o characterize the incidence, clinical features and genetics of ETV6-ABL1 leukemias, representing targetable kinase-activating lesions, we analyzed 44 new and published cases of ETV6-ABL1-positive hematologic malignancies [22 cases of acute lymphoblastic leukemia (13 children, 9 adults) and 22 myeloid malignancies (18 myeloproliferative neoplasms, 4 acute myeloid leukemias)]. The presence of the ETV6-ABL1 fusion was ascertained by cytogenetics, fluorescence in-situ hybridization, reverse transcriptase-polymerase chain reaction and RNA sequencing. Genomic and gene expression profiling was performed by single nucleotide polymorphism and expression arrays. Systematic screening of more than 4,500 cases revealed that in acute lymphoblastic leukemia ETV6-ABL1 is rare in childhood (0.17% cases) and slightly more common in adults (0.38%). There is no systematic screening of myeloproliferative neoplasms; however, the number of ETV6-ABL1-positive cases and the relative incidence of acute lymphoblastic leukemia and myeloproliferative neoplasms suggest that in adulthood ETV6-ABL1 is more common in BCR-ABL1-negative chronic myeloid leukemia-like myeloproliferations than in acute lymphoblastic leukemia. The genomic profile of ETV6-ABL1 acute lymphoblastic leukemia resembled that of BCR-ABL1 and BCR-ABL1-like cases with 80% of patients having concurrent CDKN2A/B and IKZF1 deletions. In the gene expression profiling all the ETV6-ABL1-positive samples clustered in close vicinity to BCR-ABL1 cases. All but one of the cases of ETV6-ABL1 acute lymphoblastic leukemia were classified as BCR-ABL1-like by a standardized assay. Over 60% of patients died, irrespectively of the disease or age subgroup examined. In conclusion, ETV6-ABL1 fusion occurs in both lymphoid and myeloid leukemias; the genomic profile and clinical behavior resemble BCR-ABL1-positive malignancies, including the unfavorable prognosis, particularly of acute leukemias. The poor outcome suggests that treatment with tyrosine kinase inhibitors should be considered for patients with this fusion.

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Section: Patientsmentioning

confidence: 99%

Characterization of leukemias with ETV6-ABL1 fusion

et al. 2016

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“…The Tel-Jak2 and Tel-Abl fusions have been reported in T-and pre-B cell acute lymphoblastic leukaemias (ALL) (Papadopoulos et al, 1995;Lacronique et al, 1997;Peeters et al, 1997;Van Limbergen et al, 2001) and in various chronic myelogenous leukaemias (CML) (Peeters et al, 1997;Van Limbergen et al, 2001;Keung et al, 2002). These proteins exhibit a constitutive kinase activity, are constitutively tyrosine phosphorylated in vivo and harbour transforming capacities in haematopoietic cell lines and mouse models (Golub et al, 1996;Lacronique et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

The Src tyrosine kinase Hck is required for Tel-Abl- but not for Tel-Jak2-induced cell transformation

et al. 2006

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“…Nine BCR-ABL1-negative CML patients with a variant ABL1 gene (9q34) rearrangement, involving fusion to ETV6 aka TEL (12p13) have been reported thus far. [1][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 Of 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).…”

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confidence: 99%