Early subclinical CNS manifestation in B-cell acute lymphoblastic leukemia modelled in vivo

Understanding the precise dynamics of ALL engraftment in patient-derived xenograft (PDX) mouse models is of major interest to preclinically evaluate novel directed therapeutics. We analyzed ALL engraftment in peripheral blood (PB), bone marrow (BM), spleen, and central nervous system (CNS) in the NOD/SCID/huALL mouse model over time using FACS to detect human CD19, MRD marker quantification, and cranial magnetic resonance imaging (MRI). Using FACS or MRD, ALL infiltration was first detected in BM and last in PB. Applying MRD, BM-ALL was detected 1-2 weeks earlier than by FACS reflecting the higher sensitivity of this method. Most interestingly, first CNS-ALL with positive MRD was detected early on, in some mice even along with BM-ALL and earlier and/or at higher levels as compared to first spleen-ALL. MRI showed first circumscribed CNS infiltrates 1-2 weeks after FACS detection and clearly enlarged meninges later on corresponding to the macroscopic presentation upon autopsy. In summary, our findings on very early CNS-ALL manifestation indicate a high and early propensity of ALL cells to manifest in the CNS and contribute to the understanding of ALL biology.

Publication History

Article published online:
12 May 2023