Translocations of retinoic acid receptor-α (), typically , are a genetic hallmark of acute promyelocytic leukemia (APL). However, because a small fraction of APL lack translocations of, we focused here on APL cases without translocation to elucidate the molecular etiology of-negative APL. We performed whole-genome sequencing, PCR, and FISH for five APL cases without translocations. Four of five-negative APL cases had translocations involving retinoic acid receptor-β () translocations, and was identified as an in-frame fusion in three cases; one case had an rearrangement detected by FISH, although the partner gene could not be identified. When transduced in cell lines, homodimerized and diminished transcriptional activity for the retinoic acid receptor pathway in a dominant-negative manner. enhanced the replating capacity of mouse bone marrow cells and inhibited myeloid maturation of human cord blood cells as did. However, the response of APL with translocation to retinoids was attenuated compared with that of , an observation in line with the clinical resistance of-positive APL to ATRA. Our results demonstrate that the majority of -negative APL have translocations, thereby forming a novel, distinct subgroup of APL. as an oncogenic protein exerts effects similar to those of, underpinning the importance of retinoic acid pathway alterations in the pathogenesis of APL. These findings report a novel and distinct genetic subtype of acute promyelocytic leukemia (APL) by illustrating that the majority of APL without RARA translocations harbor RARB translocations. .

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ADORA2A rs2298383 and high cumulative dose of systemic MTX administration were significantly associated with MTX-related leukoencephalopathy. Our results indicate that pharmacological intervention within the adenosine pathway may be both a treatment and preventative option for MTX-related leukoencephalopathy.

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Acute promyelocytic leukemia (APL) is cytogenetically characterized by the t(15;17) (q24;q21), although cases without this translocation exist. These cases are referred to as “cryptic” or “masked” translocations. Additionally, fewer than 5% of APL cases have another partner gene fused to the RARA gene. The TBL1XR1‐RARA fusion gene has recently been reported as a novel RARA‐associated fusion gene. We report a case with TBL1XR1‐RARA and a masked translocation that was not detected by conventional tests for RARA‐associated translocations. Three‐year‐old girl was diagnosed with APL based morphological findings, although conventional tests for RARA‐associated chimeric genes were negative. She received all‐trans retinoic acid treatment, but that was not effective. She achieved a complete remission (CR) by conventional multidrug chemotherapy, but had extramedullary relapse 2 years after onset. She underwent cord blood transplantation (CBT) in her second CR and is currently alive. To investigate the underlying pathogenesis of this unique case, we performed whole‐genome sequencing and found a cryptic insertion of RARA gene into the TBL1XR1 gene. The transcript of the chimeric gene, TBL1XR1‐RARA, was confirmed as an in‐frame fusion by RT‐PCR. In conclusion, we found using next‐generation sequencing (NGS) a TBL1XR1‐RARA fusion in a child with variant APL without the classic karyotype. Cryptic insertion could also occur in cases other than APL with PML‐RARA. Variant APL has many variants and NGS analysis should therefore be considered for APL variant cases, even for those without RARA translocation detected by conventional analysis.

Polymorphisms in VKORC1 partially affected daily warfarin dosage requirements. VKORC1 genotype and height are the primary determinants influencing warfarin dosage in Japanese pediatric patients. Further studies with larger sample sizes are needed to confirm our results.

Clear cell sarcoma of the kidney (CCSK) is the second most common renal malignancy in children. The prognosis is poorer in CCSK than in Wilms' tumor, and multimodal treatment including surgery, intensive chemotherapy, and radiation is required to improve the outcome for children with CCSK. Histological evaluation is required for the diagnosis. However, biopsies of tumors to obtain diagnostic specimens are not routinely performed because of the risk of spreading tumor cells during the procedure. Recently, internal tandem duplication (ITD) of BCOR has been recognized as a genetic hallmark of CCSK. We herein established a novel BCOR-ITD-specific polymerase chain reaction method with well-designed primers, and then performed a liquid biopsy for cell-free DNA (cfDNA) obtained from plasma of three children with nonmetastatic renal tumors (stage II) and from one control. BCOR-ITD was positively detected in the cfDNA of two cases, both of which were later diagnosed as CCSK based on histological feature of the resected tumor specimen, while it was not detected for a normal control and a patient diagnosed with Wilms' tumor. Our study is the first one of preoperative circulating tumor DNA assay in pediatric renal tumors. The liquid biopsy method enables less invasive, preoperative diagnosis of CCSK with no risk of tumor spillage, which can avoid iatrogenic upstaging.

Infant acute lymphoblastic leukemia with lysine (K)-specific methyltransferase 2A (KMT2A) rearrangements usually has a poor prognosis regardless of the fusion partners of KMT2A. However, the prognosis of pediatric acute myeloid leukemia (AML) with KMT2A rearrangements depends on its translocation partners. We herein report the case of a 9-month-old boy with a