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. 2025 Feb 21;2(2):100079.
doi: 10.1016/j.bneo.2025.100079. eCollection 2025 May.

A novel 3-way translocation involving ETV6:: IL3 drives AML with eosinophilia

Affiliations

A novel 3-way translocation involving ETV6:: IL3 drives AML with eosinophilia

Ariel Siegel et al. Blood Neoplasia. .
No abstract available

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Conflict of interest statement

Conflict-of-interest disclosure: J.M. receives research funding paid to the institution from Incyte, Novartis, Celgene, Bristol Myers Squibb (BMS), Kartos, Karyopharm, PharmaEssentia, AbbVie, Geron, CTI BioPharma; and consulting fees from Incyte, Kartos, Karyopharm, Geron, Roche, AbbVie, CTIBiotech, GlaxoSmithKline (GSK), Pfizer, PharmaEssentia, Galecto, Celgene, BMS, and Novartis. D.T. receives contracted research funding paid to his institution from CTI BioPharma, Astellas Pharma, and Gilead; and consulting fees from CTI BioPharma, Novartis, AbbVie, Sierra Oncology, GSK, and Cogent Biosciences. J.F. receives contracted research funding paid to his institution from Syros Pharmaceuticals and ORYZON. M.K. receives research funding paid to the institution from Incyte, Celgene, BMS, MorphoSys, Protagonist, Ionis, Silence Therapeutics, Kura Oncology; and consulting fees from Incyte, AbbVie, MorphoSys, and Protagonist. The remaining authors declare no competing financial interests.

Figures

Figure 1.
Figure 1.
IL-3 associated AML pathology, cytogenetics, and clonal evolution. (A) BM pathology. The BM at diagnosis was essentially replaced by myeloid blasts with no increase in eosinophils. (B) CD117 immunostain, and (C) aspirate smear. (D) Fish plot of best interpreted clone evolution based on FISH percentages and variant allele frequencies. Red arrows indicate relapse 1, black and gray arrows indicate chemotherapy, and green arrows indicate relapse 2. (E) PB white blood cell count (WBC, blue) and eosinophil percentage (% Eos, red). Arrows and time course as in panel D. “+” indicates initial presentation WBC 243× 103/μL. (F) Peripheral blood (PB) eosinophilia. (G) A BM biopsy and (H) aspirate demonstrating eosinophilia with increased blasts (arrow). (I) Cytogenetic results. Top, AML karyotype with t(5;12;15) arrows indicating t(5;12) ETV6::IL3. Bottom, Composite destained FISH karyotype with concurrent IL3 break-apart probe and a NU98-NSD1 translocation probe. From chromosome 5, 3’IL3 is translocated to chromosome 12 and NSD1 is translocated to chromosome 11. A portion of the original NUP98 reciprocal translocation on chromosome 5 moved with 3’IL3 to chromosome 12. Thus, both translocations occur in the same cell.
Figure 2.
Figure 2.
Cytokine dysregulation in IL-3 over-expression, clonal evolution, and association with other leukemia subtypes. (A) IL-3, IL-5, and IL-18 levels in PB and BM samples from case patient at relapse (Rel) and after chemotherapy, along with nonrelated AML and normal (N) cases. See arrows as in Figure 1D. (B) IL3 quantitative polymerase chain reaction (qPCR) with relative expression of messenger RNA (mRNA) from the case patient and nonrelated AML and normal cases. (C) Interphase FISH on isolated Siglec-8+ eosinophils with IL3 (red) and ETV6 (green) demonstrating translocation (yellow). (D) Flow cytometry plot of CD123 and CD34 at diagnosis and relapse, leukemia cells are marked in brown. (E) Top, interphase FISH on PB B-cell ALL with IL3 (red) and IGH (green) with translocation (yellow). Bottom, PB smear demonstrating eosinophilia (arrow), inset lymphoid blast. (F) IL3, ETV6, IL3Ra, p21, and RPN1 qPCR with relative expression of mRNA from patient’s relapsed AML BM mononuclear cells treated with vehicle (Veh), JQ1, ABBV 744, or Ruxolitinib (Rux) at 1μM for 18 hours. (∗P < .05 vs Veh).

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References

    1. Naymagon L, Marcellino B, Mascarenhas J. Eosinophilia in acute myeloid leukemia: overlooked and underexamined. Blood Rev. 2019;36:23–31. - PubMed
    1. Pulsoni A, Iacobelli S, Bernardi M, et al. M4 acute myeloid leukemia: the role of eosinophilia and cytogenetics in treatment response and survival. The GIMEMA experience. Haematologica. 2008;93(7):1025–1032. - PubMed
    1. Gotlib J, Cools J. Five years since the discovery of FIP1L1-PDGFRA: what we have learned about the fusion and other molecularly defined eosinophilias. Leukemia. 2008;22(11):1999–2010. - PubMed
    1. De Braekeleer E, Douet-Guilbert N, Morel F, Le Bris MJ, Basinko A, De Braekeleer M. ETV6 fusion genes in hematological malignancies: a review. Leuk Res. 2012;36(8):945–961. - PubMed
    1. Zaliova M, Moorman AV, Cazzaniga G, et al. Characterization of leukemias with ETV6-ABL1 fusion. Haematologica. 2016;101(9):1082–1093. - PMC - PubMed

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