Page 91 - Haematologica April 2020

ARHGEF12 in erythropoiesis of chemotherapy patients
loss. There is evidence to suggest that: (i) ANAX7 is relat- ed to erythrocyte death;34 (ii) EPB4215,16 is related to hered- itary spherocytosis in which eryptosis is an important cause of anemia; (iii) CHPT16 and BSG11,12 may be related to the vulnerability of RBC to chemotherapy; and (iv) ABCC4,17 a membrane transporter, is related to accumula- tion of cytotoxic agents in cells and chemo-sensitivity of hematopoietic cells. Other direct or indirect evidence
A
based on the known functions of the gene products sug- gests that the remaining genes in the top ten list of GWAS in our study, TFDP2, LPIN2, TNS1, RAP1GAP, ARHGEF12, could also be related to impaired hematopoiesis in response to chemotherapy.
Erythropoiesis is a tightly regulated process in which the hemoglobin level is maintained in a narrow window between 135g/L and 155g/L under normal conditions or in
B
C
Figure 5. STAT1 expression rescues the erythroid differentiation phenotype by arhgef12 knockdown in zebrafish. (A) O-Dianisidine staining results of embryos injected with control morpholino (MO) (a), arhgef12a & arhgef12b MO (b), and arhgef12a & arhgef12b MO with stat1a mRNA (c) at 4dpf. Yolk sac ventral views of the indicated microinjected embryos (a’-c’). Whole-mount in situ hybridization (WISH) results of αe1-globin in the embryos injected with control MO (e), arhgef12a & arhgef12b MO (f), and arhgef12a and arhgef12b MO with stat1a mRNA (g) at 4dpf and the corresponding magnifications of CHT (e’-g’). (B) Wright-Giemsa results of erythrocytes, which were isolated from control MO (a), arhgef12a and arhgef12b MO (b), and arhgef12a & arhgef12b MO with stat1a mRNA (c) injected embryos at 4 dpf. (C) WISH results of gata1 in the embryos injected with control MO (a), stat1a MO (b) at 4dpf and the corresponding magnifications of CHT (a’,b’). WISH results of αe1-globin in the embryos injected with control MO (c), stat1a MO (d) at 4dpf and the corresponding magnifications of CHT (c’,d’).
haematologica | 2020; 105(4)
933