Pediatric Bilateral Hypoplastic Kidney Complicated With C1q Nephropathy: A Case Report.

Progressive kidney dysfunction is often observed in children with bilateral hypoplastic kidneys. While glomerulopathy can exacerbate hypoplastic kidney progression, only IgA nephropathy and post-streptococcal acute glomerulonephritis have been noted in such cases. Herein, we present a case of a four-year-old female patient with bilateral hypoplastic kidney, kidney dysfunction, and significant proteinuria (urinary protein/creatinine ratio > 1 g/gCr), prompting referral owing to persistent hematuria since two years of age. Enalapril was initiated; however, urinary findings exhibited no improvement despite stable symptoms and kidney function. Subsequently, a kidney biopsy was performed at six years of age, and C1q nephropathy was diagnosed. Given the presence of only mild mesangial proliferation, steroids were not administered; enalapril treatment was continued. By seven years of age, the patient's hematuria had resolved, and proteinuria levels had decreased. On the latest follow-up at 12 years of age, kidney function was preserved with only mild proteinuria. This case report highlights the favorable prognosis of asymptomatic C1q nephropathy characterized by mild mesangial proliferation, even in patients with hypoplastic kidneys, renal dysfunction, and significant proteinuria. It emphasizes the significance of timely pathological evaluation for guiding appropriate interventions in such patients.

Mother-child correlation of kidney function: data from the Yamanashi Adjunct Study of Japan Environment and Children's Study (JECS).

BACKGROUND: Individual variation in kidney function can be affected by both congenital and acquired factors, and kidney function in children is possibly correlated with that in their mothers. However, the mother-child correlation in kidney function remains directly unconfirmed. METHODS: We conducted a cross-sectional study of 655 healthy pairs of 7- or 8-year-old children and their mothers as an adjunct study of a nationwide epidemiological study (Japan Environment and Children's Study). RESULTS: Both serum creatinine level (all children, r = 0.324, p < 0.001; girls, r = 0.365, p < 0.001; boys, r = 0.278, p < 0.001) and estimated glomerular filtration rate (eGFR) (r = 0.274, p < 0.001; r = 0.352, p < 0.001; r = 0.195, p < 0.001, respectively) in children were weakly associated with their maternal values. In the single linear regression analyses, maternal values of serum creatinine and eGFR were significantly associated with the children's values. Moreover, several body composition values in children, such as weight-SDS, fat (%), and predicted muscle weight, were also significantly associated with kidney function values in children. In the multiple linear regression analysis for serum creatinine levels in children, in which weight-SDS and predicted muscle weight in children were selected as adjustment factors, maternal serum creatinine level showed a significant positive association (B = 0.214, p < 0.001 in the adjusted model). Moreover, in the multiple linear regression analysis for eGFR value in children, in which fat (%) and predicted muscle weight in children were selected as adjustment factors, maternal eGFR values showed a significant positive association (B = 0.319, p < 0.001). CONCLUSIONS: We directly confirmed mother-child correlations in both serum creatinine levels and eGFR values, particularly in girls. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information.

Clinical Usefulness of T-Cell Receptor Vß Repertoire Analysis for Differentiating Multisystem Inflammatory Syndrome in Japanese Children From Toxic Shock Syndrome and Kawasaki Disease.

The specific expansion of T-cell receptor ß chain variable region (TCR-Vß21.3 + ) CD4 + and CD8 + T cells was observed in Japanese patients with multisystem inflammatory syndrome in children. In contrast, these findings were not observed in patients with toxic shock syndrome and Kawasaki disease. T-cell receptor ß chain variable region repertoire analysis to detect specific expansion of Vß21.3 + T cells might be useful for differentiating multisystem inflammatory syndrome in children from toxic shock syndrome and Kawasaki disease.

Refractive Error and Axial Length and Their Related Factors in 8-Year-Old Japanese Children: The Yamanashi Adjunct Study of the Japan Environment and Children's Study (JECS).

PURPOSE: To investigate the distribution of visual acuity, refractive error, and axial length in 8-year-old children who participated in an additional survey in Yamanashi Prefecture of the Japan Environmental Children's Study (hereafter referred to as JECS-Y) conducted from 2019 to 2021. PARTICIPANTS AND METHODS: Eight-year-old children who participated in the JECS-Y study were subjected to noncycloplegic measurements of refractive error and axial length. If the uncorrected visual acuity was less than 20/20, the best corrected visual acuity was evaluated in accordance with the autorefraction data. A questionnaire was administered regarding the parent's history of eyeglass wear or contact lens use. RESULTS: Among the 400 participating children, the rate of uncorrected visual acuity of 20/20 or better in both eyes was 70.4%. The mean equivalent spherical equivalent error for both eyes was -0.366 ± 1.016 D. The mean axial length was 23.08 ± 0.225 mm in all patients. The males showed significantly longer axial length than the females despite no differences in body height. There was a significant correlation between axial length, spherical refractive, and uncorrected visual acuity. The children of parents with a history of wearing eyeglasses or contact lenses showed a significantly more myopic equivalent refractive error than those without a history. CONCLUSIONS: This study clarified the current state of refractive error in 8-year-old children and the association of inheritance with refractive error. In addition, the axials were significantly longer in male patients.

Clinical significance of serum cytokine profiles for differentiating between Kawasaki disease and its mimickers.

OBJECTIVES: To investigate the clinical significance of serum cytokine profiles for differentiating between Kawasaki disease (KD) and its mimickers. METHODS: Patients with KD, including complete KD, KD shock syndrome (KDSS), and KD with macrophage activation syndrome (KD-MAS), and its mimickers, including multisystem inflammatory syndrome in children, toxic shock syndrome, and Yersinia pseudotuberculosis infection, were enrolled. Serum levels of interleukin (IL)-6, soluble tumor necrosis factor receptor type II (sTNF-RII), IL-10, IL-18, and chemokine (C-X-C motif) ligand 9 (CXCL9) were measured using enzyme-linked immunosorbent assay and compared them with clinical manifestations. RESULTS: Serum IL-6, sTNF-RII, and IL-10 levels were significantly elevated in patients with KDSS. Serum IL-18 levels were substantially elevated in patients with KD-MAS. Patients with KD-MAS and KD mimickers had significantly elevated serum CXCL9 levels compared with those with complete KD. Area under the receiver operating characteristic curve analysis showed that serum IL-6 was the most useful for differentiating KDSS from the others, IL-18 and CXCL9 for KD-MAS from complete KD, and CXCL9 for KD mimickers from complete KD and KD-MAS. CONCLUSION: Serum cytokine profiles may be useful for differentiating between KD and its mimickers.

Relationship between floating toes condition and lower limb muscle weight in 8-year-old children: the Yamanashi adjunct study of the Japan Environment and Children's Study (JECS-Y).

[Purpose] Floating toe is a condition in which the toes make insufficient contact with the ground. Weak muscle strength is reportedly one cause of floating toe. However, little evidence exists regarding the relationship between foot muscle strength and floating toe. Here we examined the relationship between foot muscle strength and floating toe by investigating the children' lower extremity muscle mass and floating toe conditions. [Participants and Methods] This cohort study enrolled 118 8-year-old children (62 females, 56 males) with recorded footprints and muscle mass evaluations using dual-energy X-ray absorptiometry. We calculated the floating toe score using the footprint. We measured the muscle weights and the muscle weights divided by the lengths of the lower limbs separately on the left and right sides using dual-energy X-ray absorptiometry. [Results] No significant correlations were observed between the floating toe score and muscle weights or muscle weights divided by lower-limb lengths for either gender or side. [Conclusion] In this study, no significant correlation was found between floating toe degree and lower limb muscle mass, suggesting that lower limb muscle strength is not the primary cause of floating toe, at least in children.

Arterial spin labeling perfusion imaging in an infant with anti-N-methyl-D-aspartate receptor encephalitis: A case report.

BACKGROUND: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is an autoimmune encephalitis characterized by complex neuropsychiatric syndromes and the presence of cerebrospinal fluid (CSF) antibodies against NMDAR. The characteristics of anti-NMDAR encephalitis in children, particularly infants, are unclear due to difficulties in neurologic assessment such as psychiatric symptoms. Additionally, subtle or non-specific findings of conventional magnetic resonance imaging (MRI) make early diagnosis even more difficult. Herein, we present the first case of infant anti-NMDAR encephalitis in which perfusion imaging demonstrated marked abnormalities and the absence of conventional MRI findings. CASE PRESENTATION: The patient was an 11-month-old boy who was admitted because of seizure and prolonged fever. He presented with involuntary movements of the mouth and tongue. Brain MRI showed no morphological abnormalities, but three-dimensional arterial spin labeling (ASL) perfusion imaging showed reduced blood flow in the left temporal and frontal regions and the right cerebellum. After that, a positive anti-NMDAR antibody test result was received. Despite treatment with IVIG and methylprednisolone, the involuntary movements and autonomic dysfunction gradually became more prominent. After rituximab administration, the clinical symptoms improved slightly, and follow-up MRI revealed diffuse brain atrophy and improvement in the balance of brain perfusion. CONCLUSIONS: To the best of our knowledge, this is the first case report of infantile anti-NMDAR encephalitis in which cerebral blood flow was evaluated using three-dimensional ASL perfusion imaging. Indeed, our case, which showed abnormalities only in ASL perfusion imaging, suggests that CBF assessment could aid in the early diagnosis of anti-NMDAR encephalitis in infants.

A cross-sectional study on the correlations between floating toe, plantar arch posture, and body composition in 8-year-old children.

BACKGROUND: Floating toe (FT): inadequately in contact with the ground and flexible flat foot (FFF) are frequently seen in children. According to some reports, inadequate foot muscle strength may cause FT or FFF.Therefore, a relationship may exist between arch formation, FT, and pedal muscle strength. This study aimed to evaluate the correlation of FT with plantar arch posture and body composition, including overall muscle mass. METHODS: We conducted our own cohort study in addition to the Japan Environment and Children's Study conducted by the Ministry of the Environment, Japan. Out of 705 eight-year-old children participating in this adjunct study, 578 with recorded footprints were included. Body composition (body weight, body fat percentage, and predicted muscle mass) was assessed using body composition analyzer. Presence of FT or FFF was evaluated using foot pressure plate. We calculated the FT score (small FT score indicates insufficient ground contact of the toes) and the Chippaux-Smirak Index (CSI) using images of the plantar footprint. RESULTS: The FT score (an indicator of FT) showed no significant correlation with CSI (an indicator of plantar arch posture). Moreover, no significant correlations between the predicted muscle mass, FT score, and CSI were observed. CONCLUSIONS: This is the first report that assessed the relationship of FT with plantar arch posture and body composition in children. This study indicated that muscle strength might not be a major factor for FT and FFF development in children.

Prevalence of floating toe and its relationship with static postural stability in children: The Yamanashi adjunct study of the Japan Environment and Children's Study (JECS-Y).

Floating toe (FT) is a frequently seen condition in which a toe is inadequately in contact with the ground. Although toes play an important role in stabilizing standing posture and walking, many aspects of the effects of FT on the body remain unclear. To our knowledge, there have been no reports about the relationship between FT and postural stability, especially in children. This study aimed to clarify the prevalence of FT and its relationship with static postural stability in children. Of the 400 children aged 8 years who participated in our cohort study, 396, who were examined for static postural stability, were included in this study. Postural stability and FT were assessed using a foot pressure plate. The sway path length of the center of pressure and the area of the ellipse defined as the size of the area marked by the center of pressure, were measured as an evaluation of static postural stability. We calculated the "floating toe score (FT score: small FT score indicates insufficient ground contact of the toes)" using the image of the plantar footprint obtained at the postural stability measurement. The rate of FT was elevated at more than 90%, and the FT score in the eyes-closed condition was significantly higher than that in the eyes-open condition in both sexes. The FT score significantly correlated with the center of pressure path and area. Our results suggest that ground contact of the toes is not directly related to static postural stability in children, but it may function to stabilize the body when the condition becomes unstable, such as when the eyes are closed.

Hybrid Schwannoma/Perineurioma: Morphologic Variations and Genetic Profiles.

To clarify the morphologic spectrum and molecular profiles of hybrid schwannoma/perineurioma (HSP), we investigated 15 tumors clinicopathologically and cytogenetically. HSP was classified into 2 morphologic types: mixed cellular and combined tumor types. The former comprising of 14 tumors mostly arose in the subcutaneous tissue of the extremities and the trunk of middle-aged adults. They were well-circumscribed and composed of elongated spindle-shaped tumor cells arranged in storiform and whorl patterns. Immunostaining revealed a mixed cellular proliferation of S-100 protein-positive and SOX10-positive Schwann cells and epithelial membrane antigen-positive, claudin 1-positive, and GLUT1-positive perineurial cells. During follow-up, no tumors were found to have recurred in any cases. In contrast, in the combined tumor type arising in the mediastinum of a young male with neurofibromatosis type 2, the intraneural perineurioma-like areas, characterized by small whorl-like structures, were present in plexiform schwannoma-like areas. No recurrence was noted in the case. Molecular analyses (array comparative genomic hybridization and fluorescence in situ hybridization) revealed LOH 22q in 2 tumors of 5 studied: one each of the mixed cellular and combined tumor types. Although the same diagnostic term, HSP, has been applied to both mixed and combined types, they should be separated from each other.

Resveratrol inhibits IL-33-mediated mast cell activation by targeting the MK2/3-PI3K/Akt axis.

Interleukin-33 (IL-33)/ST2-mediated mast cell activation plays important roles in the pathophysiology of allergic diseases. Hence, pharmacologically targeting the IL-33/ST2 pathway in mast cells could help to treat such diseases. We found that resveratrol inhibits IL-33/ST2-mediated mast cell activation. Resveratrol suppressed IL-33-induced IL-6, IL-13, and TNF-α production in mouse bone marrow-derived mast cells (BMMCs), mouse fetal skin-derived mast cells, and human basophils. Resveratrol also attenuated cytokine expression induced by intranasal administration of IL-33 in mouse lung. IL-33-mediated cytokine production in mast cells requires activation of the NF-κB and MAPK p38-MAPK-activated protein kinase-2/3 (MK2/3)-PI3K/Akt pathway, and resveratrol clearly inhibited IL-33-induced activation of the MK2/3-PI3K/Akt pathway, but not the NF-κB pathway, without affecting p38 in BMMCs. Importantly, resveratrol inhibited the kinase activity of MK2, and an MK2/3 inhibitor recapitulated the suppressive effects of resveratrol. Resveratrol and an MK2/3 inhibitor also inhibited IgE-dependent degranulation and cytokine production in BMMCs, concomitant with suppression of the MK2/3-PI3K/Akt pathway. These findings indicate that resveratrol inhibits both IL-33/ST2-mediated and IgE-dependent mast cell activation principally by targeting the MK2/3-PI3K/Akt axis downstream of p38. Thus, resveratrol may have potential for the prevention and treatment of broad ranges of allergic diseases.

Endometrial carcinoma in a 14-year-old: A case report.

•We present a case of endometrial carcinoma (EC) in a 14-year-old girl with no risk factors for EC.•The patient received MPA therapy and endometrial curettage.•At 47 weeks after her last MPA treatment, she has had no recurrence.•EC should be considered in diagnosing juveniles with sustained abnormal uterine bleeding, even those without risk factors.

Diagnostic Utility and Limitations of Immunohistochemistry of p16, CDK4, and MDM2 and Automated Dual-color In Situ Hybridization of MDM2 for the Diagnosis of Challenging Cases of Dedifferentiated Liposarcoma.

The diagnosis of dedifferentiated liposarcoma (DDLPS) is challenging when an atypical lipomatous tumor component is absent or obscure. To analyze the utility and limitations of ancillary techniques, we studied 11 cases of DDLPS in challenging conditions and 17 cases of nonlipogenic high-grade sarcomas with immunohistochemistry (IHC) for p16, CDK4, and MDM2 and automated dual-color in situ hybridization (DISH) for MDM2 amplification. All DDLPS specimens lacked clear lipogenic components and were immunoreactive for p16, CDK4, and MDM2. DISH analyses also revealed high-level amplification of MDM2 in all DDLPS. In contrast, among nonlipogenic sarcomas, p16, CDK4, and MDM2 were expressed in 8, 9, and 3 cases, respectively. MDM2 amplification was detected in 3 of 8 studied. The MDM2-amplified tumors were the same as the MDM2-immunoreactive tumors. After careful reevaluation of these 3 sarcomas, 2 were reclassified as DDLPS because small areas of lipogenic components were detected in the original specimens. The respective sensitivities and specificities of these markers were as follows: p16 IHC (100% and 60%), CDK4 IHC (100% and 53.3%), MDM2 IHC (100% and 93.3%), and MDM2 DISH (100% and 83.3%). The results of MDM2 IHC completely coincided with those of MDM2 DISH. The present study confirmed the substantial utility of MDM2 IHC and MDM2 DISH in the diagnosis of DDLPS, especially when lipogenic components were indistinct compared with IHC for p16 and CDK4. Furthermore, automated DISH was more practical than fluorescent in situ hybridization.

A review of clinical characteristics and genetic backgrounds in Alport syndrome.

Alport syndrome (AS) is a progressive hereditary renal disease that is characterized by sensorineural hearing loss and ocular abnormalities. It is divided into three modes of inheritance, namely, X-linked Alport syndrome (XLAS), autosomal recessive AS (ARAS), and autosomal dominant AS (ADAS). XLAS is caused by pathogenic variants in COL4A5, while ADAS and ARAS are caused by those in COL4A3/COL4A4. Diagnosis is conventionally made pathologically, but recent advances in comprehensive genetic analysis have enabled genetic testing to be performed for the diagnosis of AS as first-line diagnosis. Because of these advances, substantial information about the genetics of AS has been obtained and the genetic background of this disease has been revealed, including genotype-phenotype correlations and mechanisms of onset in some male XLAS cases that lead to milder phenotypes of late-onset end-stage renal disease (ESRD). There is currently no radical therapy for AS and treatment is only performed to delay progression to ESRD using nephron-protective drugs. Angiotensin-converting enzyme inhibitors can remarkably delay the development of ESRD. Recently, some new drugs for this disease have entered clinical trials or been developed in laboratories. In this article, we review the diagnostic strategy, genotype-phenotype correlation, mechanisms of onset of milder phenotypes, and treatment of AS, among others.

Chromophobe renal cell carcinoma with sarcomatoid differentiation containing various heterologous components.

Renal cell carcinoma (RCC) occasionally has sarcomatoid differentiation and rarely contains heterologous components. We report a case of chromophobe RCC with sarcomatoid differentiation that had various heterologous components including a unique lipomatous area. The patient was an 83-year-old woman with a palpable mass in the left lower abdomen. Grossly, the tumor was 14 cm in diameter and had yellowish-to-whitish color with focal necrosis and hemorrhage. Histologically, the tumor was composed of an eosinophilic subtype of chromophobe RCC with sarcomatoid differentiation including mainly chondrosarcoma, some osteosarcoma and a lipomatous area. The heterologous components of sarcomatoid RCC are usually osteosarcoma or chondrosarcoma, and sarcomatoid RCC with multiple heterologous components is extremely rare.

Urinary fibrin/fibrinogen degradation products measured using an anti-fibrinogen antibody predict orthostatic proteinuria.

BACKGROUND: The aim of this study was to assess the diagnostic value of urinary fibrin/fibrinogen degradation products (uFDP) measured using an anti-fibrinogen antibody in patients with orthostatic proteinuria (OP), and their use in differentiating between OP and glomerulonephritis (GN). METHODS: uFDP were measured using first urine in the morning (supine) and non-first urine during a hospital visit (upright) and then normalized to urine creatinine (uFDP/Cr, ng/mgCr). We compared (i) OP patients (n = 16); (ii) those in remission from nephrotic syndrome (NS, n = 14) and from GN (IgA nephropathy [IgAN], n = 14; Henoch-Schönlein purpura nephritis [HSPN], n = 12); and (iii) those with active GN (IgAN, n = 12; HSPN, n = 19). RESULTS: The uFDP/Cr ratio increased from supine to upright urine in patients with OP (P < 0.001), but decreased in one case. uFDP were excreted in supine urine in 94% of OP patients, with no excretion in NS remission patients or in 92% of GN remission patients (P < 0.001 for both). uFDP/Cr in supine urine was similar between the OP and active GN patients (P = 0.40), whereas proteinuria in supine urine was in the normal range in all OP patients, but was significantly higher in upright urine in the OP patients (P < 0.001). In upright urine, urinary protein/creatinine ratio was significantly lower in patients with OP than in those with active GN (P = 0.005). A uFDP/Cr ratio cut-off of 1,108 ng/mgCr in upright urine correctly differentiated OP from active GN, with a sensitivity of 87.5% and a specificity of 100%. CONCLUSION: Comparison of uFDP levels in supine/upright urine can be reliable for diagnosing OP and for differentiating it from active GN.

CRISPR/Cas9-mediated mutagenesis of the dihydroflavonol-4-reductase-B (DFR-B) locus in the Japanese morning glory Ipomoea (Pharbitis) nil.

CRISPR/Cas9 technology is a versatile tool for targeted mutagenesis in many organisms, including plants. However, this technique has not been applied to the Japanese morning glory (Ipomoea [Pharbitis] nil), a traditional garden plant chosen for the National BioResource Project in Japan. We selected dihydroflavonol-4-reductase-B (DFR-B) of I. nil, encoding an anthocyanin biosynthesis enzyme, as the target gene, and changes in the stem colour were observed during the early stages of plant tissue culture by Rhizobium [Agrobacterium]-mediated transformation. Twenty-four of the 32 (75%) transgenic plants bore anthocyanin-less white flowers with bi-allelic mutations at the Cas9 cleavage site in DFR-B, exhibiting a single base insertion or deletions of more than two bases. Thus, these results demonstrate that CRISPR/Cas9 technology enables the exploration of gene functions in this model horticultural plant. To our knowledge, this report is the first concerning flower colour changes in higher plants using CRISPR/Cas9 technology.

Dedifferentiated Liposarcoma Masquerading as Rhabdomyosarcoma.

We present a rare case of retroperitoneal dedifferentiated liposarcoma (DDLPS) masquerading as rhabdomyosarcoma. The patient was a 74-year-old man, complaining a loss of appetite. Abdominal computed tomography revealed a retroperitoneal mass, 10 cm in diameter, between the liver and the right adrenal gland. The tumor was resected and histologically diagnosed as conventional DDLPS, in which dedifferentiated component was highly cellular and composed of pleomorphic anaplastic cells. After 3 years, the tumor recurred in the right retroperitoneal space. The recurrent tumor consisted of 2 components: lipogenic and nonlipogenic. The latter differ from the dedifferentiated component of the primary tumor. The tumor cells were small, round to ovoid cells with monomorphous, round, hyperchromatic nuclei, and scant cytoplasm. Interestingly, they were diffusely positive for myogenin and desmin. To rule out the possibility of the second primary, we performed fluorescence in situ hybridization to detect FOXO1 rearrangement. We failed to demonstrate splits of the probes. In contrast, high-level amplification of MDM2 was detected by dual-color in situ hybridization. Given the morphologic and molecular findings, the neoplasm was identified as a peculiar DDLPS mimicking rhabdomyosarcoma. Retroperitoneal rhabdomyosarcoma-like tumors of adults, therefore, should be distinguished carefully from DDLPS. It could be challenging when lipogenic component was absent, but in situ molecular analyses can be helpful.

Clinical characteristics and prognosis of acute myeloid leukemia associated with DNA-methylation regulatory gene mutations.

In recent years, it has been reported that the frequency of DNA-methylation regulatory gene mutations - mutations of the genes that regulate gene expression through DNA methylation - is high in acute myeloid leukemia. The objective of the present study was to elucidate the clinical characteristics and prognosis of acute myeloid leukemia with associated DNA-methylation regulatory gene mutation. We studied 308 patients with acute myeloid leukemia. DNA-methylation regulatory gene mutations were observed in 135 of the 308 cases (43.8%). Acute myeloid leukemia associated with a DNA-methylation regulatory gene mutation was more frequent in older patients (P<0.0001) and in patients with intermediate cytogenetic risk (P<0.0001) accompanied by a high white blood cell count (P=0.0032). DNA-methylation regulatory gene mutation was an unfavorable prognostic factor for overall survival in the whole cohort (P=0.0018), in patients aged ≤70 years, in patients with intermediate cytogenetic risk, and in FLT3-ITD-negative patients (P=0.0409). Among the patients with DNA-methylation regulatory gene mutations, 26.7% were found to have two or more such mutations and prognosis worsened with increasing number of mutations. In multivariate analysis DNA-methylation regulatory gene mutation was an independent unfavorable prognostic factor for overall survival (P=0.0424). However, patients with a DNA-methylation regulatory gene mutation who underwent allogeneic stem cell transplantation in first remission had a significantly better prognosis than those who did not undergo such transplantation (P=0.0254). Our study establishes that DNA-methylation regulatory gene mutation is an important unfavorable prognostic factor in acute myeloid leukemia.