CD34 expression predicts an adverse outcome in patients with NPM1-positive acute myeloid leukemia

Dang, Harry; Chen, Yan; Kamel‐Reid, Suzanne; Brandwein, Joseph; Chang, Hong

doi:10.1016/j.humpath.2013.03.007

Cited by 26 publications

(26 citation statements)

References 31 publications

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“…1 CD34 had prognostic value in the present group of 706 patients by applying cut-offs used in literature (Kanda et al, 2000;Dang et al, 2013;Zhu et al, 2013). However, upon increasing cut-off levels the prognostic value was gradually lost.…”

Section: Discussionmentioning

confidence: 64%

“…After having established the definition of CD34-positivity and negativity, the prognostic relevance of CD34 was investigated and compared with the cut-offs used in the literature, i.e. 5%, 10% and 20%, and which did not include assessment of neoplastic character (Kanda et al, 2000;Dang et al, 2013;Zhu et al, 2013). The use of our new definition for CD34-positivity in AML revealed a difference in response to treatment: 12% of the CD34-negative cohort (19/158) never achieved CR (NCR) as compared to 22% (121/548) of the CD34-positive patients (P = 0Á005).…”

Section: Prognostic Relevance Of Cd34 Expressionmentioning

confidence: 99%

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Absence of leukaemic CD34⁺ cells in acute myeloid leukaemia is of high prognostic value: a longstanding controversy deciphered

Zeijlemaker

Wouters

Valk³

et al. 2015

Br J Haematol

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SummaryPrimary resistance and relapses after initial successful treatment are common in acute myeloid leukaemia and therefore outcome remains poor. More accurate risk group stratification and effective personalized risk adapted treatment are necessary to improve outcome. In the last two decades, controversial results have been published concerning the prognostic relevance of CD34 expression. In this study of 706 acute myeloid leukaemia patients, we established a new flow cytometric-based CD34-definition, without use of cut-off values. We discriminated CD34-positive (n = 548) and CD34-negative (n = 158) patients by the presence or absence of neoplastic CD34+ cells, respectively. CD34-status was defined using aberrant immunophenotypes and validated using molecular phenotypes. This new definition of CD34 enables strong prediction of treatment outcome in the entire patient group and in several risk subgroups. Previously observed discrepancies in prognostic impact of CD34 protein expression using cut-offs (5-20%) can now entirely be explained by considering the number of CD34-negative cases. In the total patient group, the absence of neoplastic CD34-positive cells is paralleled by low levels of minimal residual disease, suggesting relative therapy sensitivity and explaining longer survival. Overall, we present CD34 surface expression as a relatively simple, powerful and independent predictor of clinical outcome, now warranting incorporation in acute myeloid leukaemia risk stratification.

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Section: Discussionmentioning

confidence: 64%

Section: Prognostic Relevance Of Cd34 Expressionmentioning

confidence: 99%

Absence of leukaemic CD34⁺ cells in acute myeloid leukaemia is of high prognostic value: a longstanding controversy deciphered

Zeijlemaker

Wouters

Valk³

et al. 2015

Br J Haematol

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“…Different surface antigens have been retrospectively evaluated to test a possible prognostic value, but the results have not been consistent, owing also to the relatively small number of patients analyzed and to the differences in the selection of patient cohorts, types of treatment, thresholds of antigen positivity, and immunophenotyping methodologies. In Table , these conflicting results are reported for the CD13, CD15, CD11b, CD34, CD117, and CD14 antigens.…”

Section: Discussionmentioning

confidence: 99%

Independent prognostic impact of CD15 on complete remission achievement in patients with acute myeloid leukemia

Chisini

Stefanizzi

Ceglie

et al. 2016

Hematological Oncology

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The prognostic role of CD15 in acute myeloid leukemia (AML) has been tested in different studies with conflicting results. To address this issue, we retrospectively evaluated a cohort of 460 AML patients of all ages with the exclusion of acute promyelocytic leukemia (M/F 243/217, median age 50.6 years [range 0.9-81.2]) intensively treated at our institute between January 1999 and December 2010. CD15 positivity was found in 171 of 406 evaluable patients (42.1%). Complete remission (CR) was achieved by 334 patients (72.6%), while 82 (17.8%) were resistant and 44 (9.6%) died during induction: the median CR duration was 15.5 months (range 0.6-176.0), with 2-year disease-free survival rate of 45.1% (95% confidence interval 39.6-50.6). The median overall survival was 14.4 months (range 0.3-177.0), with 2-year overall survival rate of 42.2% (95% confidence interval 37.5-46.9). At univariate analysis for CR achievement, age < 60 years (P < .001), World Health Organization classification (P = .045), low-risk karyotype (P < .001), no high-risk karyotype (P = .006), positivity for AML-ETO (P = .004)/CBFβ-MYH11 (P = .003)/CD15 (P = .006)/CD11b (P = .013), negativity for FLT3-ITD (P = .001), Hb > 8 g/dL (P = .020), and white blood cell < 50 × 10 /L (P = .034) had a favorable impact. At a multivariate logistic regression model, CD15 positivity (P = .002), age < 60 years (P = .008), white blood cell < 50 × 10 /L (P = .017), and low-risk/no high-risk karyotype (P = .026/P = .025) retained an independent prognostic role on CR achievement. The baseline assessment of CD15 positivity appears to have a role in the risk evaluation for CR achievement in AML patients undergoing intensive chemotherapy and should be assessed in prospective studies together with other clinical and biologic features already reported.

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“…34 It has also been reported that CD34 expression on blast cells was also associated with poor prognosis in NPM1-mutated patients. 35,36 The pattern of miRNA expression in CD34-positive cells has been the subject of a few studies. In their study, Georgantas et al found that 33 miRNAs are expressed in CD34 HSCs collected from normal bone marrow and mobilized peripheral blood stem cells in humans.…”

Section: Cd34mentioning

confidence: 99%

Low expression of miR‐204 is associated with expression of CD34 and poor performance status in denovo AML

Abdelhafiz

El-Sayed

Saber

et al. 2020

Int J Lab Hematology

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AML is the most common type of acute leukemia in adults, accounting for approximately 80% of adult cases of acute leukemia. 1 AML is generally recognized as disease of late age, with first-time diagnoses of AML made at 68 years of age on average. 2 Still, children account for 6% to 7% of cases of AML and have a biology that is quite different from that of adult patients. 3The disease arises from bone marrow stem cells which proliferate uncontrollably with impaired differentiation capacity, leading Abstract Introduction: Acute myeloid leukemia (AML) is the most common acute leukemia in adults. There is growing evidence that microRNAs (miRNAs) provide prognostic information in AML. MiR-204 has a tumor suppressor function, and several studies have proven its role in solid cancers. The aim of this work is to evaluate the level of expression of miR-204 in adults newly diagnosed with AML with normal karyotype and to correlate its level of expression with disease outcome and different prognostic factors. Patients and methods: The study included 87 adult patients newly diagnosed with AML. Detection of miR-204 was done using RT-PCR in patients and seven agematched controls. Results: Acute myeloid leukemia patients showed significantly lower miR-204 expression, compared to control group (P = .029). Low miR-204 expression was significantly associated with positive CD34 (P = .017), with poor performance status (PS) (P = .009), and with the presence of diabetes mellitus (DM) (P = .014). Low expression of miR-204 was also significantly associated with shorter overall survival (OS) (P = .020) and disease-free survival (DFS) (P = .013). Low miR-204 expression was identified as an independent prognostic factor for prediction of shorter OS (P = .034) and DFS (P = .027) in AML. Conclusion: To the best of our knowledge; this is the first time to prove the correlation between miR-204 expression and CD34 expression. Further study of this correlation is needed to confirm the role of miR-204 in CD34-positive cells, including leukemic stem cells. This correlation may have therapeutic implications. MiR-204 can be used as a biomarker for PS in AML patients. K E Y W O R D S acute myeloid leukemia, CD34, leukemic stem cells, miR-204, performance status S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Abdelhafiz AS, Elsayed GM, Saber MM, Gameel A, Hamdy N. Low expression of miR-204 is associated with expression of CD34 and poor performance status in denovo AML. Int J Lab Hematol. 2020;42:263-269.

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CD34 expression predicts an adverse outcome in patients with NPM1-positive acute myeloid leukemia

Cited by 26 publications

References 31 publications

Absence of leukaemic CD34⁺ cells in acute myeloid leukaemia is of high prognostic value: a longstanding controversy deciphered

Absence of leukaemic CD34⁺ cells in acute myeloid leukaemia is of high prognostic value: a longstanding controversy deciphered

Independent prognostic impact of CD15 on complete remission achievement in patients with acute myeloid leukemia

Low expression of miR‐204 is associated with expression of CD34 and poor performance status in denovo AML

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CD34 expression predicts an adverse outcome in patients with NPM1-positive acute myeloid leukemia

Cited by 26 publications

References 31 publications

Absence of leukaemic CD34+ cells in acute myeloid leukaemia is of high prognostic value: a longstanding controversy deciphered

Absence of leukaemic CD34+ cells in acute myeloid leukaemia is of high prognostic value: a longstanding controversy deciphered

Independent prognostic impact of CD15 on complete remission achievement in patients with acute myeloid leukemia

Low expression of miR‐204 is associated with expression of CD34 and poor performance status in denovo AML

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Absence of leukaemic CD34⁺ cells in acute myeloid leukaemia is of high prognostic value: a longstanding controversy deciphered

Absence of leukaemic CD34⁺ cells in acute myeloid leukaemia is of high prognostic value: a longstanding controversy deciphered