Expression of cyclins D1, D2 and D3 and Ki-67 in human leukemia

Jaroslav, Polák; Hradcová, Martina; Schwarz, Jiřı́; Klamová, Hana; Stöckbauer, Petr; Kozák, Tomáš; Julius, Müller; Haškovec, C

doi:10.1080/10428190500215100

Cited by 17 publications

(11 citation statements)

References 37 publications

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“…Although the majority of CLL cells from most patients express cell cycle-related markers, low percentages of Ki-67-expressing cells have been found in the blood of patients with CLL [3]. The data derived from tissue microarrays suggest that most CLL cells are in late G1 phase (cyclin Eþ) and a significant number of cells are in the S (cyclin Aþ) and G2/M phases (cyclin B1þ) of the cell cycle [4].…”

Section: Introductionmentioning

confidence: 96%

Spontaneous apoptosis and proliferation detected by BCL-2 and CD71 proteins are important progression indicators within ZAP-70 negative chronic lymphocytic leukemia

Poeta

Principe

Maurillo

et al. 2009

Leukemia & Lymphoma

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In chronic lymphocytic leukemia (CLL), inhibition of spontaneous apoptosis determines a worse prognosis and increasing evidences show that disease progression relies also upon cycling CLL cells. We investigated bcl-2, as measure of apoptosis, and CD71, as measure of proliferation, by flow cytometry in 265 patients with CLL. Combining bcl-2 with CD71 values, we defined three subgroups: (1) bcl2 - CD71-; (2) bcl2 + CD71+; and (3) bcl2 + CD71- or bcl2- CD71+. Both a shorter progression-free survival (PFS) and overall survival (OS) were observed in ZAP-70+ (p < 0.00001) and in patients with bcl2 + CD71+ (p < 0.00001 and p = 0.02). The patients with discordant in bcl2 + CD71- and bcl2- CD71+ showed an intermediate outcome. Noteworthy, patients with bcl2 + CD71+ showed a shorter PFS within ZAP-70 negative subgroup (p = 0.00009). In multivariate analysis of PFS, age (p = 0.005), beta-(2) microglobulin (B(2)-M) (p = 0.003), bcl-2 (p = 0.004), CD49d (p = 0.001), and ZAP-70 (p < 0.001) resulted to be significant prognostic factors. The independent prognostic significance of B(2)-M (p = 0.009) and bcl-2 (p = 0.03) was confirmed within ZAP-70 negative patients. Bcl-2 and CD71 can be considered as interesting progression indicators, which should be validated in an independent cohort of patients, to take timely therapeutic decisions in CLL.

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Section: Introductionmentioning

confidence: 96%

Spontaneous apoptosis and proliferation detected by BCL-2 and CD71 proteins are important progression indicators within ZAP-70 negative chronic lymphocytic leukemia

Poeta

Principe

Maurillo

et al. 2009

Leukemia & Lymphoma

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“…IGF1R is a tyrosine kinase regulating cell growth and survival. Considering that CCND2, CCND1, and IGFR1R are frequently up-regulated in B-CLL and diffuse large B-cell lymphoma (DLBCL) (16)(17)(18)(19)(20)(21), it makes perfect sense to find them directly targeted by miR-15b/16-2. To validate this putative targeting, we assessed all these three proteins by Western blot (WB).…”

Section: Significancementioning

confidence: 99%

miR-15b/16-2 deletion promotes B-cell malignancies

Lovat

Fassan

Gasparini

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

102

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The central role of the microRNA (miR) 15a/16-1 cluster in B-cell oncogenesis has been extensively demonstrated, with over twothirds of B-cell chronic lymphocytic leukemia characterized by the deletion of the miR-15a/16-1 locus at 13q14. Despite the wellestablished understanding of the molecular mechanisms occurring during miR-15a/16-1 dysregulation, the oncogenic role of other miR-15/16 family members, such as the miR-15b/16-2 cluster (3q25), is still far from being elucidated. Whereas miR-15a is highly similar to miR-15b, miR-16-1 is identical to miR-16-2; thus, it could be speculated that both clusters control a similar set of target genes and may have overlapping functions. However, the biological role of miR-15b/16-2 is still controversial. We generated miR-15b/16-2 knockout mice to better understand the cluster's role in vivo. These mice developed B-cell malignancy by age 15-18 mo with a penetrance of 60%. At this stage, mice showed significantly enlarged spleens with abnormal B cell-derived white pulp enlargement. Flow cytometric analysis demonstrated an expanded CD19+ CD5+ population in the spleen of 40% knockout mice, a characteristic of the chronic lymphocytic leukemia-associated phenotype found in humans. Of note, miR-15b/16-2 modulates the CCND2 (Cyclin D2), CCND1 (Cyclin D1), and IGF1R (insulin-like growth factor 1 receptor) genes involved in proliferation and antiapoptotic pathways in mouse B cells. These results are the first, to our knowledge, to suggest an important role of miR-15b/16-2 loss in the pathogenesis of B-cell chronic lymphocytic leukemia.miRNAs | miR-15b | chronic lymphocytic leukemia | B cells | murine models M icroRNAs (miRNAs) are a class of small noncoding RNAs that modulate gene expression in many physiological and pathological conditions (1). Altered miRNA expression has been reported in several human cancers, and miRNA expression profiles vary according to the considered tumor (2).A role for miRNAs in tumorigenesis and progression was originally documented for the miR-15/16 family (2-5). This group of miRNAs encompasses the miR-15a/16-1 cluster (on chromosome 13q14,) the miR-15b/16-2 cluster (on chromosome 3q25), and the miR-195/497 cluster (on chromosome 17p13).The role of the miR-15a/16-1 cluster in B-cell pathology has been extensively demonstrated (5). The deletion of the miR-15a/ 16-1 cluster has been reported in over two-thirds of B-cell chronic lymphocytic leukemias (B-CLLs) (5). Our group has demonstrated that the loss of miR-15a/16-1 expression induces higher levels of the antiapoptotic proteins BCL2 and myeloid cell leukemia sequence 1 (BCL2-related) (MCL1) (3, 6). Moreover, this deletion promotes mature B-cell expansion by deregulating the transition from G1 to S phase (7).On the other hand, the biological role of miR-15b/16-2 is still controversial, as this cluster has been reported to behave as either a tumor suppressor [acute promyelocytic leukemia (8, 9) and osteosarcoma (10)] or an oncogene [melanoma (11), upregulated in the plasma of colorectal cancer (12) and...

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“…In agreement with previous studies, [13,[19][20][21], we found over expression of cyclin D1 and Ki-67 in ALL patients. On the other hand, [22] we did not detect any elevation of cyclin D1 level among their ALL patient group (0/24).…”

Section: Discussionmentioning

confidence: 71%

“…The quantitative real time RT-PCR technique appears to be the most suitable method for that purpose [22].…”

Section: Discussionmentioning

confidence: 99%

Expression of P-glycoprotein, Cyclin D1 and Ki-67 in Acute Lymphoblastic Leukemia: Relation with Induction Chemotherapy and Overall Survival

El-Sayed

Ismail

Moneer

2011

Indian J Hematol Blood Transfus

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Previous studies showed that non-cycling cells have a higher multidrug resistance (MDR) expression, which may be down-regulated by proliferation induction. Triggering these cells into proliferation down-regulates high MDR expression. The aim of this study was to determine the expression of P-glycoprotein (PGP) and cell cycle parameters (cyclin D1 and Ki-67) in acute lymphoblastic leukemia (ALL) at diagnosis, and to evaluate the correlation between the expressions of each marker, and the clinical significance of such expression with response to induction chemotherapy and overall survival. A total of 78 newly diagnosed ALL patients were enrolled in our study. PGP, cyclin D1 and Ki-67 were determined by flow cytometry. PGP expression was encountered in 10/78 (12.8%) of ALL cases. Cyclin D1 and Ki-67 were expressed in 16/77 (20.6%) and 27/76 (34.6%) of ALL cases, respectively. None of the parameters were associated with response to induction chemotherapy and overall survival. Based on the current analysis, we conclude that a joint immunophenotypic evaluation of PGP and cell cycle parameters like that adopted in this study is unlikely to reveal mechanisms of multidrug resistance associated with the clinical outcome.

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Expression of cyclins D1, D2 and D3 and Ki-67 in human leukemia

Cited by 17 publications

References 37 publications

Spontaneous apoptosis and proliferation detected by BCL-2 and CD71 proteins are important progression indicators within ZAP-70 negative chronic lymphocytic leukemia

Spontaneous apoptosis and proliferation detected by BCL-2 and CD71 proteins are important progression indicators within ZAP-70 negative chronic lymphocytic leukemia

miR-15b/16-2 deletion promotes B-cell malignancies

Expression of P-glycoprotein, Cyclin D1 and Ki-67 in Acute Lymphoblastic Leukemia: Relation with Induction Chemotherapy and Overall Survival

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