Hematopoietic stem cell involvement in BCR-ABL1-positive ALL as a potential mechanism of resistance to blinatumomab therapy

We present 2 BCR-ABL1 fusion–positive BCP-ALL patients with CD19– myeloid lineage relapse after blinatumomab therapy and show BCR-ABL1 positivity in their hematopoietic stem cell (HSC)/progenitor/myeloid compartments at initial diagnosis by fluorescence in situ hybridization after cell sorting. By using the same approach with 25 additional diagnostic samples from patients with BCR-ABL1–positive BCP-ALL, we identified HSC involvement in 40% of the patients. Patients (6 of 8) with major BCR-ABL1 transcript encoding P210BCR-ABL1 mainly showed HSC involvement, whereas in most of the patients (9 of 12) with minor BCR-ABL1 transcript encoding P190BCR-ABL1, only the CD19+ leukemia compartments were BCR-ABL1 positive (P = .02). Our data are of clinical importance, because they indicate that both CD19+ cells and CD19– precursors should be targeted to avoid CD19– relapses in patients with BCR-ABL1–positive ALL.

Source: Blood - November 2, 2017 Category: Hematology Authors: Nagel, I., Bartels, M., Duell, J., Oberg, H.-H., Ussat, S., Bruckmueller, H., Ottmann, O., Pfeifer, H., Trautmann, H., Gökbuget, N., Caliebe, A., Kabelitz, D., Kneba, M., Horst, H.-A., Hoelzer, D., Topp, M. S., Cascorbi, I., Siebert, R., Bru0 Tags: Immunobiology and Immunotherapy, Lymphoid Neoplasia, Brief Reports Source Type: research