BMI1 gene expression in myeloid leukemias and its impact on prognosis

Saudy, Niveen; Fawzy, Iman M.; Azmy, Emad; Goda, Enas F.; Eneen, Asmaa; Salam, Eman M. Abdul

doi:10.1016/j.bcmd.2014.07.002

Cited by 42 publications

(51 citation statements)

References 22 publications

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“…It is worth noting that BMI1 expression is significantly upregulated in CML patients' CD34 + cells, compared with healthy controls [13]. This finding is particularly evident during a blastic crisis [27]. Most notably, in vitro results demonstrated that BCR-ABL upregulation increases BMI1 expression, thus suggesting that BMI1 is positively regulated by BCR-ABL [13], and that BMI1 cooperates with BCR-ABL during disease progression [28].…”

Section: Discussionmentioning

confidence: 97%

Polycomb Genes are Associated with Response to Imatinib in Chronic Myeloid Leukemia

et al. 2015

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Aim: Imatinib is a tyrosine kinase inhibitor that has revolutionized the treatment of chronic myeloid leukemia (CML). Despite its efficacy, about a third of patients discontinue the treatment due to therapy failure or intolerance. The rational identification of patients less likely to respond to imatinib would be of paramount clinical relevance. We have shown that transmembrane transporter hOCT1 genotyping predicts imatinib activity. In parallel, Polycomb group genes (PcGs) are epigenetic repressors implicated in CML progression and in therapy resistance. Patients & methods: We measured the expression of eight PcGs in paired pre-and post-imatinib bone marrow samples from 30 CML patients. Results: BMI1, PHC3, CBX6 and CBX7 expression was significantly increased during imatinib treatment. Post-treatment levels of CBX6 and CBX7 predicted 3-month response rate. Measurement of post-treatment BMI1 levels improved the predictive power of hOCT1 genotyping. Conclusion: These results suggest that the expression levels of PcGs might be useful for a more accurate risk stratification of CML patients.

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Section: Discussionmentioning

confidence: 97%

Polycomb Genes are Associated with Response to Imatinib in Chronic Myeloid Leukemia

et al. 2015

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“…High expression of Bmi1 has so far been observed in myelodysplastic syndrome (MDS) [57,58], acute myeloid leukemia (AML) [59,60], chronic myeloid leukemia (CML) [61,62], and various types of lymphoma including diffuse large B cell lymphoma (DLBCL) [63][64][65][66], and has been shown to be correlated with poor prognosis. Recently, IG-BMI1 has been identified as a new fusion gene that is acquired in the advanced stage of chronic lymphocytic leukemia (CLL) and up-regulates expression of Bmi1 [67].…”

Section: Prc1 Members In Hematological Malignanciesmentioning

confidence: 99%

The roles of Polycomb group proteins in hematopoietic stem cells and hematological malignancies

Takamatsu-Ichihara¹,

Kitabayashi²

2016

Int J Hematol

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“…BMI1 (the parental gene of BMI1P1 ), a stem cell factor, was observed to be highly expressed in various types of human cancers [23, 36], including AML [37]. It was reported that BMI1 was essential for leukemic reprogramming of myeloid progenitor cells (BM blasts) into leukemic stem cells [38] and played a crucial role in regulating the proliferative activity of leukemic stem and progenitor cells [21].…”

Section: Discussionmentioning

confidence: 99%

Pseudogene BMI1P1 expression as a novel predictor for acute myeloid leukemia development and prognosis

et al. 2016

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The BMI1P1 levels of 144 de novo AML patients and 36 healthy donors were detected by real-time quantitative PCR (RQ-PCR). BMI1P1 was significantly down-regulated in AML compared with control (P < 0.001). A receiver operating characteristic (ROC) curve revealed that BMI1P1 expression could differentiate patients with AML from control subjects (AUC = 0.895, 95% CI: 0.835–0.954, P < 0.001). The percentage of blasts in bone marrow (BM) was significantly lower in BMI1P1 high-expressed group versus low-expressed group (P = 0.008). BMI1P1 high-expressed cases had significantly higher complete remission (CR) than BMI1P1 low-expressed cases (P = 0.023). Furthermore, Kaplan–Meier demonstrated that both whole AML cohort and non-M3-AML patients with low BMI1P1 expression showed shorter leukemia free survival (LFS, P = 0.002 and P = 0.01, respectively) and overall survival (OS, P < 0.001 and P = 0.011, respectively) than those with high BMI1P1 expression. Multivariate analysis also showed that BMI1P1 over-expression was an independent favorable prognostic factor for OS in both whole and non-M3 cohort of AML patients (HR = 0.462, 95% CI = 0.243–0.879, P = 0.019 and HR = 0.483, 95% CI = 0.254–0.919, P = 0.027). To further investigate the significance of BMI1P1 expression in the follow-up of AML patients, we monitored the BMI1P1 level in 26 de novo AML patients and found that the BMI1P1 level increased significantly from the initial diagnosis to post-CR (P < 0.001). These results indicated that BMI1P1 might contribute to the diagnosis of AML and the assessment of therapeutic effect.

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BMI1 gene expression in myeloid leukemias and its impact on prognosis

Cited by 42 publications

References 22 publications

Polycomb Genes are Associated with Response to Imatinib in Chronic Myeloid Leukemia

Polycomb Genes are Associated with Response to Imatinib in Chronic Myeloid Leukemia

The roles of Polycomb group proteins in hematopoietic stem cells and hematological malignancies

Pseudogene BMI1P1 expression as a novel predictor for acute myeloid leukemia development and prognosis

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