The Eckert group - ALL Relapse: Diagnostics and Research

MRD - Minimal residual disease

Remaining leukemic cells that persist in the body of patients after treatment are called minimal residual disease (MRD). These cells are very hard to detect and are the major cause of relapses in these patients. It is believed that these cells were able to resist initial therapy by developing drug resistance(s).

MRD Diagnostics

Dr. Eckert's lab is in charge of the molecular genetics diagnostics laboratory for MRD diagnostic in Close collaboration with the current ALL-REZ BFM study conducted with the Pediatric Hematology and Oncology department at the Charité.

Publications (for a complete list, click here)

Izraeli S, Eckert C.Targeted therapy of CNS leukemia? Blood. 2017 Aug 3;130(5):562-563. doi: 10.1182/blood-2017-06-788430.

Hof J, Kox C, Groeneveld-Krentz S, Bandapalli OR, Karawajew L, Schedel K, Kunz JB, Eckert C, Ludwig WD, Ratei R, Rhein P, Henze G, Muckenthaler MU, Kulozik AE, von Stackelberg A, Kirschner-Schwabe R. NOTCH1 mutation, TP53 alteration and myeloid antigen expression predict outcome heterogeneity in children with first relapse of T-cell acute lymphoblastic leukemia. Haematologica. 2017 Jul;102(7):e249-e252. doi: 10.3324/haematol.2016.157792.

van der Velden VH, de Launaij D, de Vries JF, de Haas V, Sonneveld E, Voerman JS, de Bie M, Revesz T, Avigad S, Yeoh AE, Swagemakers SM, Eckert C, Pieters R, van Dongen JJ. New cellular markers at diagnosis are associated with isolated central nervous system relapse in paediatric B-cell precursor acute lymphoblastic leukaemia. Br J Haematol. 2016 Mar;172(5):769-81. doi: 10.1111/bjh.13887.

Li B, Li H, Bai Y, Kirschner-Schwabe R, Yang JJ, Chen Y, Lu G, Tzoneva G, Ma X, Wu T, Li W, Lu H, Ding L, Liang H, Huang X, Yang M, Jin L, Kang H, Chen S, Du A, Shen S, Ding J, Chen H, Chen J, von Stackelberg A, Gu L, Zhang J, Ferrando A, Tang J, Wang S, Zhou BB. Negative feedback-defective PRPS1 mutants drive thiopurine resistance in relapsed childhood ALL. Nat Med. 2015 Jun;21(6):563-71. doi: 10.1038/nm.3840.

Karawajew L(1), Dworzak M(2), Ratei R(3), Rhein P(4), Gaipa G(5), Buldini B(6), Basso G(6), Hrusak O(7), Ludwig WD(3), Henze G(4), Seeger K(4), von Stackelberg A(4), Mejstrikova E(7), Eckert C(4). Minimal residual disease analysis by eight-color flow cytometry in relapsed childhood acute lymphoblastic leukemia. Haematologica. 2015 Jul;100(7):935-44. doi: 10.3324/haematol.2014.116707.

Eckert C(1), Hagedorn N(1), Sramkova L(2), Mann G(3), Panzer-Grümayer R(3), Peters C(3), Bourquin JP(4), Klingebiel T(5), Borkhardt A(6), Cario G(7), Alten J(7), Escherich G(8), Astrahantseff K(1), Seeger K(1), Henze G(1), von Stackelberg A(1).Monitoring minimal residual disease in children with high-risk relapses of acute lymphoblastic leukemia: prognostic relevance of early and late assessment. Leukemia. 2015 Aug;29(8):1648-55. doi: 10.1038/leu.2015.59.

Irving J(1), Matheson E(1), Minto L(1), Blair H(1), Case M(1), Halsey C(2), Swidenbank I(3), Ponthan F(1), Kirschner-Schwabe R(4), Groeneveld-Krentz S(4), Hof J(4), Allan J(1), Harrison C(1), Vormoor J(1), von Stackelberg A(4), Eckert C(4). Ras pathway mutations are prevalent in relapsed childhood acute lymphoblastic leukemia and confer sensitivity to MEK inhibition. Blood. 2014 Nov 27;124(23):3420-30. doi: 10.1182/blood-2014-04-531871.

Bokemeyer A, Eckert C, Meyr F, Koerner G, von Stackelberg A, Ullmann R, Türkmen S, Henze G, Seeger K.Copy number genome alterations are associated with treatment response and outcome in relapsed childhood ETV6/RUNX1-positive acute lymphoblastic leukemia. Haematologica. 2014 Apr;99(4):706-14. doi: 10.3324/haematol.2012.072470.

Meissner B, Bartram T, Eckert C, Trka J, Panzer-Grümayer R, Hermanova I, Ellinghaus E, Franke A, Möricke A, Schrauder A, Teigler-Schlegel A, Dörge P, von Stackelberg A, Basso G, Bartram CR, Kirschner-Schwabe R, Bornhäuser B, Bourquin JP, Cazzaniga G, Hauer J, Attarbaschi A, Izraeli S, Zaliova M, Cario G, Zimmermann M, Avigad S, Sokalska-Duhme M, Metzler M, Schrappe M, Koehler R, Te Kronnie G, Stanulla M. Frequent and sex-biased deletion of SLX4IP by illegitimate V(D)J-mediated recombination in childhood acute lymphoblastic leukemia. Hum Mol Genet. 2014 Feb 1;23(3):590-601. doi: 10.1093/hmg/ddt447. Epub 2013 Sep17.

Tzoneva G, Perez-Garcia A, Carpenter Z, Khiabanian H, Tosello V, Allegretta M, Paietta E, Racevskis J, Rowe JM, Tallman MS, Paganin M, Basso G, Hof J, Kirschner-Schwabe R, Palomero T, Rabadan R, Ferrando A. Activating mutations in the NT5C2 nucleotidase gene drive chemotherapy resistance in relapsed ALL. Nat Med. 2013 Mar;19(3):368-71. doi: 10.1038/nm.3078

Eckert C, Henze G, Seeger K, Hagedorn N, Mann G, Panzer-Grümayer R, Peters C, Klingebiel T, Borkhardt A, Schrappe M, Schrauder A, Escherich G, Sramkova L, Niggli F, Hitzler J, von Stackelberg A.J Use of allogeneic hematopoietic stem-cell transplantation based on minimal residual disease response improves outcomes for children with relapsed acute lymphoblastic leukemia in the intermediate-risk group. Clin Oncol. 2013 Jul 20;31(21):2736-42. doi: 10.1200/JCO.2012.48.5680.

Eckert C, von Stackelberg A, Seeger K, Groeneveld TW, Peters C, Klingebiel T, Borkhardt A, Schrappe M, Escherich G, Henze G.Minimal residual disease after induction is the strongest predictor of prognosis in intermediate risk relapsed acute lymphoblastic leukaemia - long-term results of trial ALL-REZ BFM P95/96. Eur J Cancer. 2013 Apr;49(6):1346-55. doi: 10.1016/j.ejca.2012.11.010.

Krentz S, Hof J, Mendioroz A, Vaggopoulou R, Dörge P, Lottaz C, Engelmann JC, Groeneveld TW, Körner G, Seeger K, Hagemeier C, Henze G, Eckert C, von Stackelberg A, Kirschner-Schwabe R. Prognostic value of genetic alterations in children with first bone marrow relapse of childhood B-cell precursor acute lymphoblastic leukemia. Leukemia. 2013 Feb;27(2):295-304. doi:10.1038/leu.2012.155.