Sensitivity to Tyrosine Kinase Inhibitors in a Human Philadelphia Chromosome-Positive (Ph+) Leukemia Model With the T315I-Inclusive Compound Mutation.

The T315I-inclusive compound mutation, the multiple mutations including the T315I mutation on the same BCR::ABL1 gene, confers resistance to diverse tyrosine kinase inhibitors (TKIs). Development of the F311I/T315I compound mutation has been reported in chronic myeloid leukemia patients who sequentially showed clinical resistance to imatinib and dasatinib. The establishment of a human leukemia model with the T315I-inclusive compound mutation remains an experimental challenge.

[HOSPITALIZATION, EDUCATION, AND OPTIMIZATION OF TOPICAL THERAPY CAN LEAD TO THE EARLY DISCONTINUATION OF ORAL JAK INHIBITORS IN ADOLESCENT SEVERE ATOPIC DERMATITIS].

In cases of moderate to severe atopic dermatitis that does not respond to topical therapy, temporary systemic administration of molecular targeted drugs (biological agents or oral Janus kinase[JAK]inhibitors) may be necessary. However, topical therapy forms the basis of the treatment for atopic dermatitis, and if topical therapy is appropriately established with long-term remission achieved, the use of molecular targeted drugs can be discontinued. In these two cases of severe adolescent atopic dermatitis, successful initiation of remission was achieved through hospitalization, disease education, skincare guidance, and the combined use of appropriate topical therapy and short-term oral JAK inhibitors during the remission induction phase.

Acquired copy number amplification at the MYC enhancer in human B-precursor acute lymphoblastic leukemia cell lines.

Our study highlights the discovery of recurrent copy number alterations in noncoding regions, specifically blood enhancer cluster (BENC-CNA), in B-precursor acute lymphoblastic leukemia (BCP-ALL) cell lines. We demonstrate that BENC-CNA acts as a super-enhancer, driving MYC expression and possibly contributing to the immortalization and proliferative advantage of BCP-ALL cells in vitro.