MLL-ENL leukemia burden initiated in femoral diaphysis and preceded by mature B-cell depletion

Abstract

The online version of this article has a Supplementary Appendix. BackgroundMolecular and cellular events that resulted in leukemia development are well characterized but initial engraftment and proliferation of leukemic cells in bone marrow and early modifications of the bone marrow microenvironment induced by engrafted leukemic cells remain to be clarified. Design and MethodsAfter retro-orbital injection of 1,000 leukemic cells expressing Mixed Lineage Leukemia-Eleven Nineteen Leukemia fusion protein in non-conditioned syngenic mice, kinetics of leukemic burden and alterations of femoral hematopoietic populations were followed using an in vivo confocal imaging sytem and flow cytometry. ResultsThree days after injection, 5% of leukemic cells were found in femurs. Little proliferation of engrafted leukemic cells could then be detected for more than two weeks while the number of femoral leukemic cells remained stable. Twenty days after injection, leukemic cells preferentially proliferated in femoral diaphysis where they formed clusters on the surface of blood vessels and bone. B220 + lymphoid cells were found near these leukemic cell clusters and this association is correlated with a decreased number of femoral B220 + IgM + cells. Increasing the number of injected leukemic cells or conditioning recipient mice with γ-irradiation resulted in leukemic cell development in diaphysis and knee. Competition experiments indicate that proliferation but not engraftment is a rate-limiting factor of leukemic cells spreading in diaphysis. Finally, 30 days after injection leukemia developed. ConclusionsAfter retro-orbital injection of 1,000 leukemic cells expressing Mixed Lineage Leukemia-Eleven Nineteen Leukemia into syngenic mice, leukemic cell burden preferentially initiates in femoral diaphysis and is preceded by changes of femoral B-lymphoid populations.Key words: MLL-ENL, leukemic cells, in vivo imaging, hematopoiesis. 2011;96(12):1770-1778. doi:10.3324/haematol.2011 This is an open-access paper. Citation: Jaracz-Ros A, Lewandowski D, Barroca V, Lavau C, and Roméo P-H. MLL-ENL leukemia burden initiated in femoral diaphysis and preceded by mature B-cell depletion. Haematologica MLL-ENL leukemia burden initiated in femoral diaphysis and preceded by mature B-cell depletionAgnieszka Jaracz-Ros, [1][2][3][4]

Speed of leukemia development and genetic diversity in xenograft models of T cell acute lymphoblastic leukemia

“…Sorted CD7 + /CD34 + and CD7 + /CD34 − cells were stained with Carboxyfluorescein Diacetate Succinimidyl Ester (CFSE) before transplantation and tracked using a Cell Vizio-instrument (Mauna Kea Technologies) to monitor their migration and adhesion to the niches into BM as developed in [13] (Figure 3A and Supplementary Figure S2). Leukemic CFSE + cells were detectable only 72h after injection, with no difference with respect to the engrafting cell number or invaded BM areas between CD7 + /CD34 + and CD7 + /CD34 − cells (Figure 3A–3C and Supplementary Figure S2B).…”

“…24 and 72h after injection, CFSE + cells were detected in the 2 femurs by fiber optic imaging as previously described [13]. Briefly, the knee of anesthetized transplanted mice was flexed and superficially pierced with a 23-gauge needle through the joint.…”