Differences in stroma cell signaling after contact to acute lymphoblastic leukemia B-cells derived from adult and pediatric patients

We previously show that protein-kinase C-β (PKC-β) orchestrates the tumor interaction with the surrounding microenvironment. Malignant B-cells in ALL and CLL induce PKC-β overexpression in bone marrow stroma cells (BMSCs), and in turn, this overexpression is required for the support provided by stromal cells to the tumor.

Mounting evidence implicates that the Lyn-kinase as key modulator of B-cell homeostasis is playing a role in maintaining the leukemic phenotype in a variety of cancers because it is involved in relevant cellular processes of hematopoietic and non-hematopoietic cells.

However, so far studies about the role of Lyn in ALL have only been conducted, neglecting the role of the leukemic microenvironment.

Here we describe that primary B-cells from different ALL subtypes impose diverse genetic changes in stromal cells. Gene expression analysis indicates that contact with B-ALL cells induce the expression of cancer stem cell genes in BMSCs depending on ALL subtypes. We detect variable cytokine profiles induced in BMSCs after contact to ALL cells derived from adult and pediatric patients. We can discriminate ALL subtypes that keep different survival support on BMSCs, particularly with regard to PKC-β deficiency.

Additionally, we describe that the contact to BMSCs sensitize ALL cells to the Lyn-kinase inhibitors, clearly depending on the ALL subtype.

Conclusively, we describe that primary B-ALL cells are able to modify BMSCs during contact that results in different gene expression, signaling pathways and cytokine levels in BMSCs depending on the ALL subtype. Interference with the PKC-β or Lyn pathway activated in the leukemia microenvironment may offer new therapeutic options to fully eradicate malignant B-cells from bone marrow niches.