Chronic myeloid leukemia (CML) is a common adult leukemia. Both the acute phase of the disease and the adverse effects of anti-cancer treatments can lead to a poor prognosis. The N

6

-methyladenine (m

6

A) modification plays an important regulatory role in various physiological and pathological processes. KIAA1429 is a known m

6

A regulator

but the biological role of KIAA1429 in CML is unclear. In this study

we observed that the m

6

A levels and KIAA1429 expression were significantly up-regulated in patients with blast phase CML. Notably

KIAA1429 regulated the total level of RNA m

6

A modification in the CML cells and promoted the malignant biological behaviors of CML cells

including proliferation

migration

and imatinib resistance. Inhibiting KIAA1429 in CML cells reduced the stability of RAB27B mRNA through the m

6

A/YTHDF1 axis

consequently inhibiting CML proliferation and drug efflux

ultimately increasing the sensitivity of CML cells to imatinib. Moreover

the knockdown of RAB27B also inhibited the proliferation and drug resistance of CML cells and promoted their apoptosis. Rucaparib

a recently developed anti-cancer agent

suppressed the expression of KIAA1429 and CML cell proliferation and promoted cell apoptosis. Rucaparib also inhibited the tumorigenesis of CML cells

in vivo

. The combined use of rucaparib and imatinib enhanced the sensitivity of CML cells to imatinib. Our study provides evidence that elevated KIAA1429 expression in the blast phase of CML enhances the stability of RAB27B mRNA through the m

6

A/YTHDF1 axis to up-regulate RAB27B expression

thereby promoting CML progression. Rucaparib exerts inhibitory effects on KIAA1429 expression and thus reduces CML progression.