Mouse Anti-Synthetic abl Oncogene Peptide Hybridoma [423-24F9]

BCR-ABL1 tyrosine kinase inhibitors (TKIs) have dramatically improved survival outcomes in patients with chronic phase chronic myeloid leukemia (CML-CP) and are associated with a manageable safety profile. However, long-term TKI administration can lead to cardiovascular or renal adverse events. One goal in discontinuation of TKIs was reduction of adverse events, but it is unclear whether chronic toxicities are ameliorated as a result. In this study, we evaluated changes in estimated glomerular filtration rate (eGFR) in patients with CML-CP before and after TKI discontinuation. Long-term TKI treatment appears to induce renal toxicity, as eGFR at the time of TKI discontinuation correlated with the duration of TKI treatment (r = - 0.478, p = 0.005). Patients who received imatinib as first-line treatment exhibited lower eGFR levels than those treated with dasatinib or nilotinib, which may be correlated with long-term treatment (p = 0.027). After TKI discontinuation, no significant increases in eGFR were seen either in patients with treatment-free remission (66.8-71.2 ml/min/1.73 m(2)) or molecular relapse (64.8-68.7 ml/min/1.73 m(2), p = 0.666). These data indicate that TKI-induced renal toxicities are associated with long-term TKI treatment, and may be irreversible even following treatment discontinuation.

Background About 50 different CALR frameshift mutations have been identified in BCR-ABL1 negative MPN, all leading to the development of common new protein C terminus. Antibody targeting this terminal epitope can be useful to identify this driver mutation using immunohistochemistry. Materials and Methods CALR mutation analysis was carried out in 51 JAK2V617F negative cases, PMF (n = 22) and ET (n = 29). PCR followed by fragment analysis was performed for molecular detection of CALR mutation. Bone marrow biopsy specimens of corresponding patients were subjected to IHC using mutation specific antibody CAL2. Staining pattern and intensity were observed. Staining of <2% of background nonmegakaryocytic (non- MK) cells were regarded as Pattern A, while staining of more than 2% of background nonmegakaryocytic (non-MK) was regarded as pattern B. Results CALR mutation was noted in 40.9% (9/22) and 41.4% (12/29) of JAK2V617F negative PMF and ET, respectively. All CALR mutated cases, irrespective of the mutation type, showed a positive IHC staining in the megakaryocytes with moderate to bright intensity. All CALR wild-type cases were negative on IHC. (Concordance rate- 100%). Pattern A was noted in 40% cases, while pattern B was noted in 60% cases. Pattern A staining had significantly higher chances of having type 1 mutation as compared to pattern B. In contrast, pattern B had a nonsignificant trend toward higher bone marrow cellularity and marrow fibrosis. Conclusion CAL2 IHC detects all types of CALR mutation. This can act as a sensitive, specific, rapid, and cost-effective screening test for CALR mutation analysis.