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Klinik für Innere Medizin IHämatologie, Onkologie und Stammzelltransplantation

Hartmann Laboratory

Microenvironment-induced therapy resistance in leukemia and lymphoma

Scientific focus

Our group is interested in how the tumor microenvironment mediates therapy resistance in leukemia and lymphoma. In particular, we address how adhesive ligands, cytokines and antigens affect the capacity of integrins to mediate tumor cell retention in protective niches. We mainly focus on the pathophysiological role of VLA-4 integrin activation in chronic lymphocytic leukemia and other hematopoietic malignancies.

 

Team

Principal Investigator

PD Dr. rer. nat. Tanja Nicole Hartmann

Tel.: +49 (0) 761 270 71511
tanja.hartmann@uniklinik-freiburg.de


Dr. rer. nat. Andrea Härzschel

Dr. rer. nat. Andrea Härzschel
Postdoctoral scientist
Tel.: +49 (0) 761 270 71920
andrea.haerzschel@uniklinik-freiburg.de

Dr. Lixia Li

Dr. rer. nat. Lixia Li
Postdoctoral scientist
Tel.: +49 (0) 761 270 71800
lixia.li@uniklinik-freiburg.de

Dr. rer. nat. Svenja Dannewitz-Prosseda
Postdoctoral scientist
svenja.dannewitz@uniklinik-freiburg.de

Laura Polcik

Laura Polcik
PhD student
Tel.: +49 (0) 761 270 71800
laura.polcik@uniklinik-freiburg.de

Danielle-Justine Danner

Danielle-Justine Danner
Technician, medical student
Tel.: +49 (0) 761 270 71920
danielle.danner@uniklinik-freiburg.de

Driti Ashok
PhD student
Tel.: +49 (0) 761 270 71920
driti.ashok@uniklinik-freiburg.de

Michael Hauerwas
Bachelor student
Tel.: +49 (0) 761 270 71920
michael.hauerwas@uniklinik-freiburg.de

Susanne Reinfeld
MD student
Tel.: +49 (0) 761 270 71920
susanne.reinfeld@uniklinik-freiburg.de

Ruth Zickermann
Bachelor Student
Tel.: +49 (0) 761 270 71511
ruth.zickermann@uniklinik-freiburg.de

Sophia Engel

Tel.: +49 (0) 761 270 71920
sophia.engel@uniklinik-freiburg.de

We are looking for a postdoctoral researcher (part time), for more information see ⇒

https://www.uniklinik-freiburg.de/karriere/stellenangebote/ausschreibungen/detailansicht/job/2287.html


New Frontiers Research Topic open for submissions

We welcome authors to contribute with Original Research and Review articles that will add to our continuing efforts to understand the intricate relationship between cell metabolism, oncogenesis and adhesion. For more information see Metabolism and Cell Adhesion in Cancer

Our previous data suggest that the leukemia cell-stroma interface may bear signaling hubs that integrate oncogenic signals and protective cues from the tumor microenvironment. Current projects study the impact of these adhesive interfaces in the context of disease progression and therapy resistance in chronic lymphocytic leukemia (CLL), acute myeloid leukemia and multiple myeloma. We are particularly interested on activation of the VLA-4 integrin by different signals derived from the hematopoietic microenvironment. We use time-lapse and real-time microscopy, flow cytometric tools combined with immunofluorescence and mouse models to characterize the contribution of adhesion to therapy resistance against novel kinase inhibitors.

Leukemia cells interact with stromal cells. This VLA-4 mediated interaction supplies the tumor cell with crucial survival and proliferation signals and eventually therapy resistance.

Different ways of integrin activation are involved in chronic lymphocytic leukemia and acute myeloid leukemia. In chronic lymphocytic leukemia, inside-out activation of the VLA-4 integrin (also known as CD29/CD49d) occurs upon antigen or chemokine stimulation in secondary lymphoid organs and involves several kinases. Expression of CD49d in this disease marks a high-risk group because this interaction contributes to therapy resistance.

In acute myeloid leukemia, CD44 critically contributes to VLA-4 activation in the bone marrow environment involving Src and other kinases.

Full publication list see: https://pubmed.ncbi.nlm.nih.gov/?term=Hartmann%20TN&page=6

Selected publications of last two years:

  1. The Importance of Tumor-Host Interactions in Adult B-Cell Leukemias and Lymphomas.
    Deaglio S, Hartmann TN.
    Int J Mol Sci. 2020
  2. CD44 engagement enhances acute myeloid leukemia cell adhesion to the bone marrow microenvironment by increasing VLA-4 avidity
    Gutjahr JC, Bayer E, Yu X, Laufer JM, Höpner JP, Tesanovic S, Härzschel A, Auer G, Rieß T, Salmhofer A, Szenes E, Haslauer T, Durand-Onayli V, Ramspacher A, Pennisi SP, Artinger M, Zaborsky N, Chigaev A, Aberger F, Neureiter D, Pleyer L, Legler DF, Orian-Rousseau V, Greil R, Hartmann TN.
    Haematologica. 2020
  3. An Updated Perspective on Current Prognostic and Predictive Biomarkers in Chronic Lymphocytic Leukemia in the Context of Chemoimmunotherapy and Novel Targeted Therapy
    Cohen JA, Bomben R, Pozzo F, Tissino E, Härzschel A, Hartmann TN, Zucchetto A, Gattei V.
    Cancers 2020
  4. VLA-4 Expression and Activation in B Cell Malignancies: Functional and Clinical Aspects
    Härzschel A, Zucchetto A, Gattei V, Hartmann TN.
    Int J Mol Sci. 2020
  5. TCL1 transgenic mice as a model for CD49d-high chronic lymphocytic leukemia
    Szenes E, Härzschel A, Decker S, Tissino E, Pischeli J, Gutjahr JC, Kissel S, Pennisi S, Höpner JP, Egle A, Zaborsky N, Dierks C, Follo M, Chigaev A, Zucchetto A, Greil R, Gattei V, Hartmann TN.
    Leukemia 2020
  6. CD49d promotes disease progression in chronic lymphocytic leukemia: new insights from CD49d bimodal expression
    Tissino E, Pozzo F, Benedetti D, Caldana C, Bittolo T, Rossi FM, Bomben R, Nanni P, Chivilò H, Cattarossi I, Zaina E, Norris K, Polesel J, Gentile M, Tripepi G, Moia R, Santinelli E, Innocenti I, Olivieri J, D'Arena G, Laurenti L, Zaja F, Pozzato G, Chiarenza A, Di Raimondo F, Rossi D, Pepper C, Hartmann TN, Gaidano G, Del Poeta G, Gattei V, Zucchetto A.
    Blood 2020
  7. Methods for Investigating VLA-4 (CD49d/CD29) Expression and Activation in Chronic Lymphocytic Leukemia and Its Clinical Applications
    Zucchetto A, Tissino E, Chigaev A, Hartmann TN, Gattei V.
    Methods Mol Biol. 2019
  8. Rac GTPases in Hematological Malignancies
    Durand-Onaylı V, Haslauer T, Härzschel A, Hartmann TN.
    Int J Mol Sci. 2018
  9. Microenvironment-induced CD44v6 promotes early disease progression in chronic lymphocytic leukemia
    Gutjahr JC, Szenes E, Tschech L, Asslaber D, Schlederer M, Roos S, Yu X, Girbl T, Sternberg C, Egle A, Aberger F, Alon R, Kenner L, Greil R, Orian-Rousseau V, Hartmann TN.
    Blood. 2018
  10. Functional and clinical relevance of VLA-4 (CD49d/CD29) in ibrutinib-treated chronic lymphocytic leukemia
    Tissino E, Benedetti D, Herman SEM, Ten Hacken E, Ahn IE, Chaffee KG, Rossi FM, Dal Bo M, Bulian P, Bomben R, Bayer E, Härzschel A, Gutjahr JC, Postorino M, Santinelli E, Ayed A, Zaja F, Chiarenza A, Pozzato G, Chigaev A, Sklar LA, Burger JA, Ferrajoli A, Shanafelt TD, Wiestner A, Del Poeta G, Hartmann TN, Gattei V, Zucchetto A.
    J Exp Med. 2018