January 2023 - Ines Garces de los Fayos Alonso

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Dr. Ines Garces de los Fayos Alonso

MedUni Wien RESEARCHER OF THE MONTH January 2023

Anaplastic large cell lymphoma (ALCL) is an aggressive non-Hodgkin T-cell lymphoma predominantly driven by a hyperactive Anaplastic Lymphoma Kinase (ALK) fusion protein. Children and young adults diagnosed with ALK+ ALCL respond positively to established treatment options however, a subset of patients relapse due to development of ALK inhibitor resistance. Previous findings from the Kenner lab have identified an alternative receptor, Platelet Derived Growth Factor Receptor Beta (PDGFRβ), which acts like an antenna on T-cells and picks up external signals. However, the underlying molecular mechanisms and the extent to which PDGFRβ contributed to malignancy remained elusive. In this study, Dr.in Garces de los Fayos Alonso and colleagues concluded that the PDGFRβ signaling axis acts as a double-edged sword, giving malignant cells a selective advantage that increases their carcinogenic potential, while simultaneously providing an alternative pathway for pharmacological inhibition in ALK+ ALCL relapse patients.

Selected Literature

1. Garces de Los Fayos Alonso I., Zujo L., Wiest I., Kodajova P., Timelthaler G., Edtmayer S., Zrimšek M., Kollmann S., Giordano C., Kothmayer M., Neubauer H.A., Dey S., Schlederer M., Schmalzbauer B.S., Limberger T., Probst C., Pusch O., Högler S., Tangermann S., Merkel O., Schiefer A.I., Kornauth C., Prutsch N., Zimmerman M., Abraham B., Anagnostopoulos J., Quintanilla-Martinez L., Mathas S., Wolf P., Stoiber D., Staber P.B., Egger G., Klapper W., Woessmann W., Look T.A., Gunning P., Turner S.D., Moriggl R., Lagger S., Kenner L. PDGFRβ promotes oncogenic progression via STAT3/STAT5 hyperactivation in anaplastic large cell lymphoma. Mol Cancer. 2022.
   doi: 10.1186/s12943-022-01640-7
   IF: 41.4

2. Sorger H., Dey S., Vieyra-Garcia P.A., Pölöske D., Teufelberger A.R., de Araujo E.D., Sedighi A., Graf R., Spiegl B., Lazzeri I., Braun T., Garces de los Fayos Alonso I., Schlederer M., Timelthaler G., Kodajova P., Pirker C., Surbek M., Machtinger M., Graier T., Perchthaler I., Pan Y., Fink-Puches R., Cerroni L., Ober J., Otte M., Albrecht J.D., Tin G., Abdeldayem A., Manaswiyoungkul P., Olaoye O.O., Metzelder M.L., Orlova A., Berger W., Wobser M., Nicolay J.P., André F., Nguyen V.A., Neubauer H.A., Fleck R., Merkel O., Herling M., Heitzer E., Gunning P.T., Kenner L., Moriggl R. and Wolf P. Blocking STAT3/5 through direct or upstream kinase targeting in leukemic cutaneous T-cell lymphoma. EMBO Mol Med. 2022. doi: 10.15252/emmm.20211520
   IF: 14.3

3. Limberger T., Schlederer M., Trachtová K., Garces de Los Fayos Alonso I., Yang J., Högler S., Sternberg C., Bystry V., Oppelt J., Tichý B., Schmeidl M., Kodajova P., Jäger A., Neubauer H.A., Oberhuber M., Schmalzbauer B.S., Pospisilova S., Dolznig H., Wadsak W., Culig Z., Turner S.D., Egger G., Lagger S., Kenner L. KMT2C methyltransferase domain regulated INK4A expression suppresses prostate cancer metastasis. Mol Cancer. 2022.
   doi: 10.1186/s12943-022-01542-8
   IF: 41.4

4. Trigg R.M., Lee L.C., Prokoph N., Jahangiri L., Reynolds C.P., Amos Burke G.A., Probst N.A., Han M., Matthews J.D., Lim H.K., Manners E., Martinez S., Pastor J., Blanco-Aparicio C., Merkel O., Garces de Los Fayos Alonso I., Kodajova P., Tangermann S., Högler S., Luo J., Kenner L., Turner S.D. The targetable kinase PIM1 drives ALK inhibitor resistance in high-risk neuroblastoma independent of MYCN status. Nat Commun. 2019.
   doi: 10.1038/s41467-019-13315-x
   IF: 17.6

5. Garces de Los Fayos Alonso I., Liang H.C., Turner S.D., Lagger S., Merkel O., Kenner L. The Role of Activator Protein-1 (AP-1) Family Members in CD30-Positive Lymphomas. Cancers (Basel). 2018.
   doi: 10.3390/cancers10040093
   IF: 6.5