Biallelic loss ofCDKN2Ais associated with poor response to treatment in pediatric acute lymphoblastic leukemia

2016 ◽  
Vol 58 (5) ◽  
pp. 1162-1171 ◽  
Author(s):  
Marcin Braun ◽  
Agata Pastorczak ◽  
Wojciech Fendler ◽  
Joanna Madzio ◽  
Bartlomiej Tomasik ◽  
...  
2021 ◽  
Vol 10 (9) ◽  
pp. 1926
Author(s):  
Hiroto Inaba ◽  
Ching-Hon Pui

The outcomes of pediatric acute lymphoblastic leukemia (ALL) have improved remarkably during the last five decades. Such improvements were made possible by the incorporation of new diagnostic technologies, the effective administration of conventional chemotherapeutic agents, and the provision of better supportive care. With the 5-year survival rates now exceeding 90% in high-income countries, the goal for the next decade is to improve survival further toward 100% and to minimize treatment-related adverse effects. Based on genome-wide analyses, especially RNA-sequencing analyses, ALL can be classified into more than 20 B-lineage subtypes and more than 10 T-lineage subtypes with prognostic and therapeutic implications. Response to treatment is another critical prognostic factor, and detailed analysis of minimal residual disease can detect levels as low as one ALL cell among 1 million total cells. Such detailed analysis can facilitate the rational use of molecular targeted therapy and immunotherapy, which have emerged as new treatment strategies that can replace or reduce the use of conventional chemotherapy.


2018 ◽  
Vol 120 (5) ◽  
pp. 7428-7438 ◽  
Author(s):  
Nashwa El‐Khazragy ◽  
Amal Ali Elshimy ◽  
Safaa Shawky Hassan ◽  
Safa Matbouly ◽  
Gehan Safwat ◽  
...  

2019 ◽  
Vol 19 ◽  
pp. S178 ◽  
Author(s):  
Nashwa El-Khazragy ◽  
Amal Ali Elshimy ◽  
Safaa Shawky Hassan ◽  
Safa Matbouly ◽  
Gehan Safwat ◽  
...  

2015 ◽  
Vol 13 (22) ◽  
pp. 6299-6312 ◽  
Author(s):  
Cara E. Toscan ◽  
Marwa Rahimi ◽  
Mohan Bhadbhade ◽  
Russell Pickford ◽  
Shelli R. McAlpine ◽  
...  

Glucocorticoids form a critical component of chemotherapy regimens for pediatric acute lymphoblastic leukemia and initial poor response to glucocorticoid therapy is predictive of inferior outcome.


Medicine ◽  
2017 ◽  
Vol 96 (44) ◽  
pp. e8511 ◽  
Author(s):  
Alireza Moafi ◽  
Mozhdeh Ziaie ◽  
Marjan Abedi ◽  
Soheila Rahgozar ◽  
Nahid Reisi ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shumaila Sayyab ◽  
Anders Lundmark ◽  
Malin Larsson ◽  
Markus Ringnér ◽  
Sara Nystedt ◽  
...  

AbstractThe mechanisms driving clonal heterogeneity and evolution in relapsed pediatric acute lymphoblastic leukemia (ALL) are not fully understood. We performed whole genome sequencing of samples collected at diagnosis, relapse(s) and remission from 29 Nordic patients. Somatic point mutations and large-scale structural variants were called using individually matched remission samples as controls, and allelic expression of the mutations was assessed in ALL cells using RNA-sequencing. We observed an increased burden of somatic mutations at relapse, compared to diagnosis, and at second relapse compared to first relapse. In addition to 29 known ALL driver genes, of which nine genes carried recurrent protein-coding mutations in our sample set, we identified putative non-protein coding mutations in regulatory regions of seven additional genes that have not previously been described in ALL. Cluster analysis of hundreds of somatic mutations per sample revealed three distinct evolutionary trajectories during ALL progression from diagnosis to relapse. The evolutionary trajectories provide insight into the mutational mechanisms leading relapse in ALL and could offer biomarkers for improved risk prediction in individual patients.


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