ZMYM3 mutation

Mutations in ZMYM3 are mainly loss-of-function, associate with NOTCH1 signaling mutations and shorten TFT in CLL patients, suggesting that ZMYM3 mutational status may be a useful marker in the management of early stage CLL patients. Moreover, ZMYM3 mutations reduce histone H4 acetylation and cooperate with NOTCH1 mutations to dysregulate gene-expression, leading to impair DNA damage response and apoptosis evasion.

In conclusion, our work shows that ZMYM3 mutations highly associate with NOTCH1 mutations and have an impact in the outcome of CLL patients, especially in early-stage cases. Moreover, we demonstrate that ZMYM3 mutations reduce histone H4 acetylation levels and alter gene expression of CLL cells, resulting in impaired DNA damage repair and promoting apoptosis evasion.

This study highlights scRNA-seq as an efficient method for tracking rare cells potent for causing CLL refractoriness, thus enabling their subsequent detailed characterization. Presented study was funded by the following grants: MH-CZ_AZV_NU20-08-00314, MEYS- CZ_MUNI/A/1224/2022, MH-CZ_RVO_65269705009, NPO_NUVR_LX22NPO5102, TACR_TN02000109. TP53, RNA-seq, B-CLL

The patient started oral imatinib 400 mg per day and achieved a complete cytogenetic response at 3 months...Then the patient was started on treatment for ISS stage II standard risk myeloma with ID regimen: ixazomib 4 mg on days 1, 8 , 15 and dexamethasone 20 mg on days 1, 8, 15 , 22 in 28-day cycles...N1 Shangcheng Road. Yiwu, Zhejiang, Peoples R China.

Deletion of THADA associates with advanced pathologic stage only. IMPLICATIONS: A higher frequency of damaging mutation in ZMYM3 causing genomic instability along with higher frequency of altered genomic regions including deletions of MAP3K7, BNIP3L, RB1, and NEIL3, and gain of MYC appear to be distinct somatically acquired genetic alterations that may contribute to more aggressive prostate cancer in AA/black men.