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CXXC5 (retinoid-inducible nuclear factor, RINF) is a potential therapeutic target in high-risk human acute myeloid leukemia.

Astori A, Fredly H, Aloysius TA, Bullinger L, Mansat-De Mas V, de la Grange P, Delhommeau F, Hagen KM, Récher C, Dusanter-Fourt I, Knappskog S, Lillehaug JR, Pendino F, Bruserud Ø - Oncotarget (2013)

Bottom Line: Furthermore, patients with low-risk cytogenetic abnormalities showed significantly lower levels compared to patients with high-risk abnormalities, and high RINF/CXXC5/ mRNA levels were associated with decreased overall survival for patients receiving intensive chemotherapy for newly diagnosed AML.This association with prognosis was seen both when investigating (i) an unselected patient population as well as for patients with (ii) normal cytogenetic and (iii) core-binding factor AML.The association with adverse prognosis together with the antiapoptotic effect of CXXC5/RINF suggests that targeting of CXXC5/RINF should be considered as a possible therapeutic strategy, especially in high-risk patients who show increased expression in AML cells compared with normal hematopoietic cells.

View Article: PubMed Central - PubMed

Affiliation: Inserm, U1016, Institut Cochin, F-75014, Paris, France.

ABSTRACT
The retinoid-responsive gene CXXC5 localizes to the 5q31.2 chromosomal region and encodes a retinoid-inducible nuclear factor (RINF) that seems important during normal myelopoiesis. We investigated CXXC5/RINF expression in primary human acute myeloid leukemia (AML) cells derived from 594 patients, and a wide variation in CXXC5/RINF mRNA levels was observed both in the immature leukemic myeloblasts and in immature acute lymphoblastic leukemia cells. Furthermore, patients with low-risk cytogenetic abnormalities showed significantly lower levels compared to patients with high-risk abnormalities, and high RINF/CXXC5/ mRNA levels were associated with decreased overall survival for patients receiving intensive chemotherapy for newly diagnosed AML. This association with prognosis was seen both when investigating (i) an unselected patient population as well as for patients with (ii) normal cytogenetic and (iii) core-binding factor AML. CXXC5/RINF knockdown in AML cell lines caused increased susceptibility to chemotherapy-induced apoptosis, and regulation of apoptosis also seemed to differ between primary human AML cells with high and low RINF expression. The association with adverse prognosis together with the antiapoptotic effect of CXXC5/RINF suggests that targeting of CXXC5/RINF should be considered as a possible therapeutic strategy, especially in high-risk patients who show increased expression in AML cells compared with normal hematopoietic cells.

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RINF expression by primary human acute leukemia cellsRINF expression was determined for primary AML cells derived from the bone marrow of 20 French patients (LEFT); primary AML cells derived from the peripheral blood of 59 Norwegian patients (MIDDLE); and for primary ALL cells derived from the blood of 16 patients (RIGHT). The median RINF level is indicated in the figure.
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Figure 1: RINF expression by primary human acute leukemia cellsRINF expression was determined for primary AML cells derived from the bone marrow of 20 French patients (LEFT); primary AML cells derived from the peripheral blood of 59 Norwegian patients (MIDDLE); and for primary ALL cells derived from the blood of 16 patients (RIGHT). The median RINF level is indicated in the figure.

Mentions: We analyzed RINF expression for 59 unselected Norwegian AML patients (Table 1). The expression showed a wide variation between patients (Fig. 1) without any significant correlations to age or gender. Samples derived from patients with de novo AML showed a slight but significant decrease of the RINF levels compared to patients with relapsed or secondary AML (Mann-Whitney's test, p<0.05). A similar median level and variation range was also seen for ALL blasts derived from 14 patients (Fig. 1).


CXXC5 (retinoid-inducible nuclear factor, RINF) is a potential therapeutic target in high-risk human acute myeloid leukemia.

Astori A, Fredly H, Aloysius TA, Bullinger L, Mansat-De Mas V, de la Grange P, Delhommeau F, Hagen KM, Récher C, Dusanter-Fourt I, Knappskog S, Lillehaug JR, Pendino F, Bruserud Ø - Oncotarget (2013)

RINF expression by primary human acute leukemia cellsRINF expression was determined for primary AML cells derived from the bone marrow of 20 French patients (LEFT); primary AML cells derived from the peripheral blood of 59 Norwegian patients (MIDDLE); and for primary ALL cells derived from the blood of 16 patients (RIGHT). The median RINF level is indicated in the figure.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3824541&req=5

Figure 1: RINF expression by primary human acute leukemia cellsRINF expression was determined for primary AML cells derived from the bone marrow of 20 French patients (LEFT); primary AML cells derived from the peripheral blood of 59 Norwegian patients (MIDDLE); and for primary ALL cells derived from the blood of 16 patients (RIGHT). The median RINF level is indicated in the figure.
Mentions: We analyzed RINF expression for 59 unselected Norwegian AML patients (Table 1). The expression showed a wide variation between patients (Fig. 1) without any significant correlations to age or gender. Samples derived from patients with de novo AML showed a slight but significant decrease of the RINF levels compared to patients with relapsed or secondary AML (Mann-Whitney's test, p<0.05). A similar median level and variation range was also seen for ALL blasts derived from 14 patients (Fig. 1).

Bottom Line: Furthermore, patients with low-risk cytogenetic abnormalities showed significantly lower levels compared to patients with high-risk abnormalities, and high RINF/CXXC5/ mRNA levels were associated with decreased overall survival for patients receiving intensive chemotherapy for newly diagnosed AML.This association with prognosis was seen both when investigating (i) an unselected patient population as well as for patients with (ii) normal cytogenetic and (iii) core-binding factor AML.The association with adverse prognosis together with the antiapoptotic effect of CXXC5/RINF suggests that targeting of CXXC5/RINF should be considered as a possible therapeutic strategy, especially in high-risk patients who show increased expression in AML cells compared with normal hematopoietic cells.

View Article: PubMed Central - PubMed

Affiliation: Inserm, U1016, Institut Cochin, F-75014, Paris, France.

ABSTRACT
The retinoid-responsive gene CXXC5 localizes to the 5q31.2 chromosomal region and encodes a retinoid-inducible nuclear factor (RINF) that seems important during normal myelopoiesis. We investigated CXXC5/RINF expression in primary human acute myeloid leukemia (AML) cells derived from 594 patients, and a wide variation in CXXC5/RINF mRNA levels was observed both in the immature leukemic myeloblasts and in immature acute lymphoblastic leukemia cells. Furthermore, patients with low-risk cytogenetic abnormalities showed significantly lower levels compared to patients with high-risk abnormalities, and high RINF/CXXC5/ mRNA levels were associated with decreased overall survival for patients receiving intensive chemotherapy for newly diagnosed AML. This association with prognosis was seen both when investigating (i) an unselected patient population as well as for patients with (ii) normal cytogenetic and (iii) core-binding factor AML. CXXC5/RINF knockdown in AML cell lines caused increased susceptibility to chemotherapy-induced apoptosis, and regulation of apoptosis also seemed to differ between primary human AML cells with high and low RINF expression. The association with adverse prognosis together with the antiapoptotic effect of CXXC5/RINF suggests that targeting of CXXC5/RINF should be considered as a possible therapeutic strategy, especially in high-risk patients who show increased expression in AML cells compared with normal hematopoietic cells.

Show MeSH
Related in: MedlinePlus