BCR (BCR Activator Of RhoGEF And GTPase)

P2, N=25, Completed, H. Lee Moffitt Cancer Center and Research Institute | Active, not recruiting --> Completed

P2, N=25, Recruiting, University of Chicago | Suspended --> Recruiting | Trial completion date: Mar 2027 --> Mar 2028 | Trial primary completion date: Mar 2027 --> Mar 2028

P2, N=20, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial completion date: Nov 2026 --> Jun 2026 | Trial primary completion date: Nov 2026 --> Jun 2026

The patient had a history of CML treated with imatinib for 4 years, with loss of complete hematological response for 3 months before being diagnosed with RCC and lung metastases. Due to a T315I mutation in the BCR-ABL1 gene, the treatment regimen included a novel combination of Axitinib, Dasatinib, and low-dose nivolumab. The patient showed a remarkable therapeutic response with a complete metabolic response accompanied by a highly significant reduction in the size of the tumor and complete resolution of the metastatic lung lesions, as well as a major molecular response in terms of CML disease control.

Overall, clinical information gained from calreticulin testing is greatest when it is used in an integrated clinicopathologic and molecular testing context rather than as a standalone test. To make calreticulin mutations more effectively used for diagnosis or prognosis in routine hematology practice, we need standardization of testing, harmonization of reporting, and prospective validation of risk-models based on both the subtypes and the burden of the mutation.

Finally, suppression of CLN7 markedly reduced tumor growth in human xenograft models without compromising normal hematopoietic function. These findings establish CLN7 as a critical regulator of leukemic cell survival, representing a promising therapeutic target for myeloid leukemia.

Other compounds that inhibited cIAP1/2 also efficiently inhibited the proliferation of CML cells. Thus, WDD-R4-tet might be a novel therapeutic agent for CML, which functions by inhibiting novel cell-survival signaling pathways generated on the mitochondrial outer membrane of CML cells.

P3, N=8, Terminated, Sarit Assouline | N=164 --> 8 | Trial completion date: Dec 2025 --> Jul 2025 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2025 --> Jul 2025; Insufficient patient accrual

P3, N=5949, Completed, National Cancer Institute (NCI) | Trial completion date: Oct 2026 --> Mar 2026 | Active, not recruiting --> Completed

Imatinib exposure in K562 cells is associated with an early Hippo pathway transcript surge followed by delayed microRNA alterations. The CD34⁺ analyses were exploratory and did not validate a uniform primary-sample Hippo-YAP response. Further functional studies are required to determine whether these microRNAs directly regulate Hippo pathway transcripts or influence leukemic cell fate.

Comparing benign hematologic tissues with CML samples revealed about 90 CML-specific peptides that became more prominent after SFK or JNK inhibition. Overall, this work provides a quantitative, multi-omic framework to rationally combine kinase inhibitors with immunotherapy to boost antigen visibility and antileukemic immunity.

In general, JAK2 V617F is an effective prognostic and diagnostic biomarker in myeloproliferative neoplasms. It can be further enhanced in diagnostic laboratory hematology with further optimization of the strategies of molecular testing, reporting systems, and multi-marker diagnostic algorithms.