We know that tumor cell microenvironment (niche) play an important role in malignant progression. The concept of “cancer stem cell niche” was firstly proposed and developed in leukemia models. Recently we’ve learned that leukemic proliferation in the bone marrow alters the stromal microenvironment and creates malignant niches that outcompete native hematopoietic progenitor cell niches for CD34+ cell engraftment. Today the concept still under investigation and discussion. There are many questions, that should be clarified in future studies:
* Do leukemic cells create a new leukemic niches or modifying already existent hematopoietic stem cell (HSC) niches?
* Do leukemic cells reorganize the molecular microenvironment specifically to entrap HSC, or is the creation of competitive HSC niches a coincidental side effect of leukemic growth?
* Is this behavior specific for leukemic cells or any cancer cells metastases in bone marrow can create abnormal niches?
* What other possible mechanisms and pathways involved? How we can manipulate of interaction leukemic cells with BM microenvironment more efficiently?
I’m very pleased to share the review The leukemic stem cell niche: current concepts and therapeutic opportunities very well written by “big mane guys”: Steven Lane, David Scadden and Gary Gilliland. This review is unique, because the only one in the field and including all recent data summary and future perspectives.
One citation about hijacking signaling pathways and link to the clinic:
Homing to the microenvironment appears important in sustaining LSC survival. LSC may also hijack these pathways in a number of ways, for example, up-regulation of the α4β1 integrin, VLA-4. Patients with undetectable VLA-4 levels on leukemic blasts had an excellent response to chemotherapy, perhaps indicating that this pathway may mediate a stromal influence on sensitivity to chemotherapy.
great open access review! highly recommended!