Clonal evolution and clinical implications of genetic abnormalities in blastic transformation of chronic myeloid leukaemia

Blast crisis (BC) predicts dismal outcomes in patients with chronic myeloid leukaemia (CML). Although additional genetic alterations play a central role in BC, the landscape and prognostic impact of these alterations remain elusive. Here, we comprehensively investigate genetic abnormalities in 136 BC and 148 chronic phase (CP) samples obtained from 216 CML patients using exome and targeted sequencing. One or more genetic abnormalities are found in 126 (92.6%) out of the 136 BC patients, including the RUNX1-ETS2 fusion and NBEAL2 mutations. The number of genetic alterations increase during the transition from CP to BC, which is markedly suppressed by tyrosine kinase inhibitors (TKIs). The lineage of the BC and prior use of TKIs correlate with distinct molecular profiles. Notably, genetic alterations, rather than clinical variables, contribute to a better prediction of BC prognosis. In conclusion, genetic abnormalities can help predict clinical outcomes and can guide clinical decisions in CML

Contribution of knee adduction moment impulse to pain and disability in Japanese women with medial knee osteoarthritis

Background: An increase in the knee adduction moment is one of the risk factors of medial knee osteoarthritis. This study examined the relationship between knee adduction moment and self-reported pain and disability. We also investigated the influence of pain on the relationships between knee adduction moment and gait performance and disability. Methods: Thirty-eight Japanese women with medial knee osteoarthritis participated in this study (6637 years (41-79 years)). Gait analysis involved the measurement of the external knee adduction moment impulse in the stance duration and during 3 subdivisions of stance. The total, pain and stiffness, and physical function Japanese Knee Osteoarthritis Measure scores were determined. Findings: The pain and stiffness, physical function, and total scores were positively correlated with the knee adduction moment impulses in the stance duration, and initial and second double support interval, and single limb support interval. The knee adduction moment impulse during the stance duration was related to the pain and stiffness subscale and gait velocity. The pain and stiffness subscale was related to the physical function subscale. Interpretation: Our results suggest that increasing in the knee adduction moment impulse, a proxy for loading on the medial compartment of the knee, is related to increased pain during weight-bearing activities such as walking, thereby restricting walking performance and causing disability by reducing gait velocity. Thus, the reduction in the knee adduction moment impulse during gait may result in pain relief and may serve as a conservative treatment option with disease-modifying potential. (C) 2010 Elsevier Ltd. All rights reserved