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Acute myeloid leukemia (AML) is a malignancy characterized by differentiation arrest of hematopoietic precursor cells. Differentiation therapy is effective for patients with acute promyelocytic leukemia; however, only a few effective differentiation therapies have been established for patients with other AML subtypes. In this study, seven benzimidazole anthelmintics were examined to determine the effects of differentiation on AML cells. The expression of monocyte markers (CD11b and CD14) was elevated after treatment with most benzimidazole anthelmintics. Among these drugs, parbendazole (PBZ) induced AML cell differentiation at low concentration. PBZ induced the monocyte marker expression, KLF4/DPYSL2A gene expression, and apoptosis for 21 AML cell lines with various subtypes and a primary AML sample. Finally, an in vivo analysis using an AML patient-derived xenograft mouse model showed a significant decrease in the chimerism level and prolonged survival in PBZ-treated mice. These findings could lead to a more effective differentiation therapy for AML. Low concentrations of the anthelmintic parbendazole (PBZ) induces monocytic differentiation in AML cells and PBZ could be a candidate for drug repositioning. [ABSTRACT FROM AUTHOR]

APL with I ZBTB16-RARA i is reported to be resistant to treatment with ATRA and ATO and exhibits a low response to conventional chemotherapy [[7], [9]]. APL is usually sensitive to all-trans retinoic acid (ATRA) therapy in combination with anthracyclines or arsenic trioxide (ATO), resulting in favorable rates of complete remission and superior overall survival. Dear Editor, Acute promyelocytic leukemia (APL) is a distinct form of acute myeloid leukemia characterized by reciprocal chromosome translocation t(15;17)(q24;q21), resulting in the production of the I PML-RARA i fusion gene [[1]]. Notably, I ZBTB16-RARA i APL is resistant to ATO and exhibits impaired sensitivity to ATRA, leading to a significantly poorer clinical outcome than patients with I PML-RARA i [[5]-[7]]. [Extracted from the article]

Summary: Differentiation therapy is a less toxic but still a very effective treatment for a subset of acute myeloid leukaemia (AML) cases. With the goal to identify novel compounds that can effectively and safely induce the terminal differentiation of non‐acute promyelocytic leukaemia (APL) AML cells, we performed a chemical screening and identified albendazole (ABZ), a widely used anti‐helminthic drug, as a promising lead compound that can differentiate non‐APL AML cells by stimulating the Krüppel‐like factor 4‐dihydropyrimidinase‐like 2A (KLF4‐DPYSL2A) differentiation axis to the monocytes. Our in vitro and in vivo findings demonstrate that ABZ is an attractive candidate drug as a novel differentiation chemotherapy for patients with non‐APL AML. [ABSTRACT FROM AUTHOR]

Abstract: Background: Gene abnormalities, particularly chromosome rearrangements generating gene fusion, are associated with clinical characteristics and prognosis in pediatric acute myeloid leukemia (AML). Karyotyping is generally performed to enable risk stratification, but the results are not always consistent with those of reverse transcription–polymerase chain reaction (RT‐PCR), and more accurate and rapid methods are required. Methods: A total of 487 samples from de novo AML patients enrolled in the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) AML‐05 study (n = 448), and from acute promyelocytic leukemia (APL) patients enrolled in the JPLSG AML‐P05 study (n = 39) were available for this investigation. Multiplex quantitative RT‐PCR was performed to detect eight important fusion genes: AML1(RUNX1)‐ETO(RUNX1T1), CBFB‐MYH11, MLL(KMT2A)‐AF9(MLLT3), MLL‐ELL, MLL‐AF6(MLLT4), FUS(TLS)‐ERG, NUP98‐HOXA9, and PML‐RARA. Results: Fusion genes were detected in 207 (46.2%) of the 448 AML‐05 patient samples. After exclusion of two samples with PML‐RARA, no chromosomal abnormalities were identified on karyotyping in 19 of 205 patients (9.3%) positive for fusion genes on RT‐PCR. Fusion genes were confirmed on fluorescence in situ hybridization (FISH) in 11 of these 19 patients. In contrast, fusion genes were detected in 37 of 39 patients (94.9%) from the AML‐P05 study, and 33 of these results were consistent with the karyotyping. There were discrepancies in four patients (10.8%), three with normal karyotypes and one in whom karyotyping was not possible. All four of these patients were PML‐RARA positive on FISH. Conclusions: Multiplex quantitative RT‐PCR‐based fusion gene screening may be effective for diagnosis of pediatric AML. [ABSTRACT FROM AUTHOR]