Prognostic Significance of SALL4 Expression Levels in Paediatric Acute Myeloid Leukaemia (AML).

Pediatric AML still represent an unfavourable disease resulting from the heterogeneous clonal expansion of malignant transformed haematopoietic stem or progenitor cell. The leukemia cell population is continuously replenish by rare, functionally distinct “leukaemia stem cells” (LSC) endowed with the capacity to self renew as well with the ability to generate clonogenic leukemic progenitors The AML-LSCs have been well documented and seem to behave like quiescent or slowly dividing hematopoietic stem cells. Therefore, LSC are considered less sensitive to treatments, which rather target actively dividing cells, and responsible for relapse. Recently, Y. Ma et al. suggested a major role of SALL4 gene both in stemness activity and leukemia transformation of normal hematopoietic stem cells. We sought to evaluate the expression of SALL4 gene in a panel of 88 pediatric AML, 60 Acute Lymphoblastic Leukemia (T and B ALL) and a few hematopoietic normal tissues. SALL4 expression was determined by quantitative RT-PCR in pre-treatment bone marrow samples (BM) (median blasts: 80%) and in normal tissues. SALL4 expression was much higher in AML compared to ALL (p 16, n= 12) had the worst outcome compared to the three others. Once stratified on MRC groups, MRC2 patients in the upper SALL4 quartile had 3.2 times more risk of relapse (HR= 3.2, CI95%: 1.3–7.8, P=0.02) and 5.4 more risk to die (HR=5.4, CI95%: 1.8–7.6; P= 0.0005) than MRC2 patients in the three others quartiles. In conclusion, SALL4 expression level may define an important risk factor in AML, particularly among patients with cytogenetic intermediate risk.