Background
Primary cutaneous CD4‐positive small/medium pleomorphic T‐cell lymphoproliferative disorder has been defined as a type of lymphoproliferative disorder with indolent clinical course and excellent prognosis, yet a precise diagnosis is still hard to reach.
Methods
A retrospective analysis of 22 patients including 16 females and six males was performed.
Results
The age of patients ranged from 5 to 79 years. The average age of all patients was 43.5, and the median age of all patients was 44.5. Two patients had multiple lesions, and others were presented with a solitary asymptomatic lesion. Besides general features, folliculotropism was observed in four cases. In addition to express CD3 and CD4, CD30 were positive to some extent. Some reactive cells could express CD8 and CD20. For follicular helper T‐cell markers, although CXCL‐13 was negative in the stained cases (18/18), the expression of PD‐1 (12/17), BCL‐6 (12/16) and CD10 (11/15) was observed in most cases. In addition, we performed T‐cell receptor (TCR) rearrangement on five patients, and all of them showed monoclonality. Nearly all patients had excellent prognosis.
Conclusions
Primary cutaneous CD4‐positive small/medium pleomorphic T‐cell lymphoproliferative disorder is complex. Some features like folliculotropism should also be noted. Besides, the expression of follicular helper T‐cell markers is not invariable. Moreover, CD8 positivity, Ki‐67 index, and lesion number were perhaps not absolute prognostic indicators. To reach a diagnosis of this rare entity, putting all the pieces together is important.
Background
A number of studies have demonstrated that N6‐methyladenosine (m6A) plays a vital role in the pathological process of various tumours. Recently, it was found that m6A writers or erasers affect the tumourigenesis of melanoma. However, the relationship between m6A readers such as YTH domain family (YTHDF) proteins and melanoma was still elusive.
Methods
RT‐qPCR, Western blot and immunohistochemistry were conducted to measure the expression level of YTH N6–methyladenosine RNA binding protein 3 (YTHDF3) and lysyl oxidase–like 3 (LOXL3) in melanoma tissues and cells. The effects of YTHDF3 and LOXL3 on melanoma were verified in vitro and in vivo. Multi‐omics analysis including RNA‐seq, MeRIP‐seq, RIP‐seq and mass spectrometry analyses was performed to identify the target. The interaction between YTHDF3 and LOXL3 was verified by RT‐PCR, Western blot, MeRIP‐qPCR, RIP‐qPCR and CRISPR‐Cas13b‐based epitranscriptome engineering.
Results
In this study, we found that m6A reader YTHDF3 could affect the metastasis of melanoma both in vitro and in vivo. The downstream targets of YTHDF3, such as LOXL3, phosphodiesterase 3A (PDE3A) and chromodomain helicase DNA‐binding protein 7 (CHD7) were identified by means of RNA‐seq, MeRIP‐seq, RIP‐seq and mass spectrometry analyses. Besides, RT‐qPCR, Western blot, RIP‐qPCR and MeRIP‐qPCR were performed for subsequent validation. Among various targets of YTHDF3, LOXL3 was found to be the optimal target of YTHDF3. With the application of CRISPR–Cas13b‐based epitranscriptome engineering, we further confirmed that the transcript of LOXL3 was captured and regulated by YTHDF3 via m6A binding sites. YTHDF3 augmented the protein expression of LOXL3 without affecting its mRNA level via the enrichment of eukaryotic translation initiation factor 3 subunit A (eIF3A) on the transcript of LOXL3. LOXL3 downregulation inhibited the metastatic ability of melanoma cells, and overexpression of LOXL3 ameliorated the inhibition of melanoma metastasis caused by YTHDF3 downregulation.
Conclusions
The YTHDF3‐LOXL3 axis could serve as a promising target to be interfered with to inhibit the metastasis of melanoma.
DEAR EDITOR, A 46-year-old woman presented with a 1-month history of plaques and nodules with ulceration on the upper arms after an injection lipolytic procedure 2 months previously (a). She initially received levofloxacin, cefprozil and ebastine at another clinic, but failed to respond. Histological examination revealed an abscess and granulomas without caseous necrosis in the middle and lower dermis (b). Ziehl-Neelsen staining showed acid-fast bacilli. Mycobacterium immunogenum was cultured and confirmed by genetic sequencing. The patient was commenced on oral clarithromycin and rifampin and had improved 2 months later (c). Mycobacterium immunogenum is a rare, nontuberculous mycobacterium resistant to standard disinfectants. Infections are usually associated with penetrating trauma and present as inflammatory papules, plaques, abscesses, nodules and ulcerations.
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