High Musashi-2 Expression Is an Unfavorable Prognostic Factor in Adult B-Cell Acute Lymphoblastic Leukemia.

Musashi-2 (MSI2) can inhibit translation of the mRNA encoding NUMB, the NOTCH signaling inhibitor, and play a vital role in the maintenance of hematopoietic stem cells. Musashi-1 (MSI1), another isoform of Musashi family, positively regulates NOTCH1 expression. Recent studies have demonstrated that MSI2 expression was up-regulated during chronic myelogenous leukemia (CML) progression and its high expression was associated with poor outcome of CML and acute myeloid leukemia (AML). However, the prognostic significance of MSI2 expression and the relation between MSI2 and NOTCH1 expressions in acute lymphoblastic leukemia (ALL) remain unknown.

In this study, real-time PCR was used to measured expression levels of MSI2 and NOTCH1 signaling related genes in 116 B-ALL and 24 T-ALL patients, in whom more than 70% leukemic cells were morphologically detected in bone morrow (BM) at diagnosis. Clinical and Molecular data in relation with MSI2 expression level were analyzed.

In our B-ALL cohort, although MSI2 expression was not associated with gender, age, white blood cell (WBC), t(9;22)/BCR-ABL and IK6 variant of IKZF1, patients with high MSI2 expression had inferior overall survival (OS) (P=0.007) and event free survival (EFS) (P=0.002) than patients with low MSI2 expression. Multivariate analysis showed that high MSI2 expression was an independently prognosic factor in OS (P=0.001, HR=2.641, 95%CI, 1.494–4.668), EFS (P<0.001, HR=2.562, 95%CI, 1.513–4.218) and RFS (P=0.043, HR=2.057, 95%CI, 1.023–4.137). Moreover, MSI2 expression level had a positive correlation with that of NOTCH1 (P<0.001), but not c-MYC (P=0.432) or HES1 (P=0.509). Similarly, NOTCH1 expression level in patients with high MSI2 expression (0.98, range 0.02 to 13.58) was significantly higher than that in patients with low MSI2 expression (0.42, range 0.01 to 3.55, P=0.001), but c-MYC and HES1 expression levels between patients with high MSI2 expression and low MSI2 expression showed no significant differences (both P>0.05).

Our data suggests MSI2 high expression can indicate poor prognosis in adult B-ALL accompanying with elevated NOTCH1 expression but not activating NOTCH1 downstream pathway.

No relevant conflicts of interest to declare.