Halving Time of BCR-ABL1 in Chronic Myeloid Leukemia: Is It Better Than Day-90 Value—A Multicenter Study From South India

2020 ◽  
Vol 20 (5) ◽  
pp. e205-e211 ◽  
Author(s):  
Shashidhar V. Karpurmath ◽  
Arun Seshachalam ◽  
Kalaiselvi Selvaraj ◽  
Priyadarshini Rajamani ◽  
Satish kumar ◽  
...  
2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Ji Hoon Jung ◽  
Tae-Rin Kwon ◽  
Soo-Jin Jeong ◽  
Eun-Ok Kim ◽  
Eun Jung Sohn ◽  
...  

Though tanshinone IIA and cryptotanshinone possess a variety of biological effects such as anti-inflammatory, antioxidative, antimetabolic, and anticancer effects, the precise molecular targets or pathways responsible for anticancer activities of tanshinone IIA and cryptotanshinone in chronic myeloid leukemia (CML) still remain unclear. In the present study, we investigated the effect of tanshinone IIA and cryptotanshinone on the Janus activated kinase (JAK)/signal transducer and activator of transcription (STAT) signaling during apoptotic process. We found that both tanshinone IIA and cryptotanshinone induced apoptosis by activation of caspase-9/3 and Sub-G1 accumulation in K562 cells. However, they have the distinct JAK/STAT pathway, in which tanshinone IIA inhibits JAK2/STAT5 signaling, whereas cryptotanshinone targets the JAK2/STAT3. In addition, tanshinone IIA enhanced the expression of both SHP-1 and -2, while cryptotanshinone regulated the expression of only SHP-1. Both tanshinone IIA and cryptotanshinone attenuated the expression of bcl-xL, survivin, and cyclin D1. Furthermore, tanshinone IIA augmented synergy with imatinib, a CML chemotherapeutic drug, better than cryptotanshinone in K562 cells. Overall, our findings suggest that the anticancer activity of tanshinone IIA and cryptotanshinone is mediated by the distinct the JAK/STAT3/5 and SHP1/2 signaling, and tanshinone IIA has the potential for combination therapy with imatinib in K562 CML cells.


Tumor Biology ◽  
2014 ◽  
Vol 35 (7) ◽  
pp. 7187-7193 ◽  
Author(s):  
Sailaja Kagita ◽  
Srihari Uppalapati ◽  
Sangeeta Jiwatani ◽  
Vijay Gandhi Linga ◽  
Sadasivudu Gundeti ◽  
...  

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 17517-17517
Author(s):  
K. V. Saini ◽  
P. Kumari ◽  
M. L. Saini ◽  
P. Latha ◽  
A. Jain ◽  
...  

17517 Background: Chronic Myeloid Leukemia (CML) is characterized by the translocation between chromosomes 9 and 22. The resulting Philadelphia chromosome is the cytogenetic hallmark of this disease. Occasionally, other variant translocations may be present. Methods: We performed a retrospective analysis of case records between 1999 and 2006 of patients diagnosed with CML at the Kidwai Memorial Institute of Oncology, a tertiary care cancer centre in South India. The cytogenetic profile of CML patients was determined. Results: The total number of CML patients (proven by bone marrow aspiration) diagnosed at our centre during the study period was 1268. Of these, 79 cases (48 M, 31 F) had variant translocations ( Table 1 ). The mean age at diagnosis was 35.9 yrs (SD 11.4). The involved chromosomes were 22 (91.1%), 9 (69.9%), 1 (13.9%), 19 (11.4%), 12 (8.8%), 7 (7.6%), and 6 (7.6%). Other involved chromosomes were 11, 2, 3 13, 15, 17, 16, 20, 21, and 8 in decreasing order of frequency. Table 1 : Cytogenetic Profile of CML Conclusions: Other than chromosomes 22 and 9, the variant translocations commonly involved chromosomes no 1, 19, 12, 7, and 6. The identification of these variant translocations and their co-relation with the clinical behavior may identify new prognostic markers. [Table: see text] No significant financial relationships to disclose.


2015 ◽  
Vol 134 (4) ◽  
pp. 248-254 ◽  
Author(s):  
Beatriz Felicio Ribeiro ◽  
Bruna Rocha Vergílio ◽  
Eliana Cristina Martins Miranda ◽  
Maria Helena Almeida ◽  
Marcia Torresan Delamain ◽  
...  

Early reduction of BCR-ABL1 transcript levels has been associated with improved outcome in chronic myeloid leukemia (CML) treatment. We evaluated 54 chronic-phase CML patients treated with imatinib who switched therapy to dasatinib (n = 33) or nilotinib (n = 21). BCR-ABL1 transcript levels were measured in peripheral blood using real-time quantitative PCR (RQ-PCR) every 3 months from the start of second-line treatment. Patients with BCR-ABL transcript levels >10% at 3 months and >1% at 6 months had significantly inferior progression-free (PFS) and event-free survival (EFS) than patients with RQ-PCR <10% at 3 months and <1% at 6 months (66 vs. 100%, p = 0.01, and 33 vs. 73%, p = 0.02, respectively). Patients with RQ-PCR <10% at 3 months and >1% at 6 months also had inferior PFS and EFS than patients with RQ-PCR <10% at 3 months and <1% at 6 months (48 vs. 100%, p = 0.002, and 25 vs. 73%, p < 0.0001, respectively). Two measurements of BCR-ABL levels were better than a single one to stratify chronic-phase CML patients as failure after second-line therapy.


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