The Changes on hematopoietic Stem Cells and mIcroenvIronment of childhood acute Lymphoblastic Leukemia at dIagnosIs and after chemotherapy

Hematopoietic microenvironment consists of endosteal and vascular microenvironment. Osteopontin and osteonectic are released by osteoblast which is one of the factors regulating endosteal microenvironment. CXCL12 and CXCR4 are included in the factors regulating vascular microenvironment. Markers indicating the degree of differentiation of hematopoietic stem cells (HSC) include CD133, CD34 and CD117. This study is to evaluate the expression pattern of markers of hematopoietic microenvironment and HSC in childhood acute lymphoblastic leukemia (ALL) at diagnosis and the changes of them after chemotherapy.

Between January, 2007 and December, 2009, 32 patients were diagnosed as ALL at Asan Medical Center. Bone marrow (BM) biopsies were obtained at diagnosis, after induction, consolidation, interim maintenance and delayed intensification. There were 22 male and 10 female patients with a mean age of 7.33 years. The diagnoses were a common cell ALL in 29. By immunohistochemistry, we analyzed the expressions of CD133, CD34, CD117, osteopontin, osteonectin, CXCL12, and CXCR4 in these BM biopsy specimens.

CD133+ cells decreased at diagnosis, and recovered after consolidation. The CD34+ cells decreased after induction, and then gradually increased again. CD117+ cells were fewer at diagnosis, but increased after chemotherapy. The expression of osteopontin was depressed at diagnosis, and gradually recovered. The expression of osteonectin was also suppressed at diagnosis and recovered after delayed intensification. CXCL12 was suppressed at diagnosis, recovered after consolidation and decreased after delayed intensification. CXCR4 was also suppressed at diagnosis, but increased after therapy.

This study is the first report on the changes of hematopoietic microenvironment and HSC of childhood ALL at diagnosis and after chemotherapy, evaluated by immunohistochemistry. CD133+ cells, CD34+ cells and CD117+ cells increased in the reconstructive phase. CD34 can be a marker reflecting the BM recovery. Proliferation of osteoblasts and stromal cells were active after interim maintenance. The reconstruction of HSC and BM matrix increased after consolidation. The recovery of BM microenvironment was established after consolidation and interim maintenance chemotherapy. These findings may serve as basic data for future studies dealing with the hematopoietic microenvironment and HSC of childhood ALL.

No relevant conflicts of interest to declare.