Combined Expression of CD34 and FLT3-Internal Tandem Duplication Mutation Predicts Poor Response to Treatment in Acute Myeloid Leukemia

被引:5
|
作者
Abdellateif, Mona S. [1 ]
Kassem, Amira B. [2 ]
EL-Meligui, Yomna M. [3 ]
机构
[1] Cairo Univ, Canc Biol Dept, Natl Canc Inst, Med Biochem & Mol Biol Unit, Cairo, Egypt
[2] Damanhour Univ, Fac Pharm, Clin Pharm & Pharm Practice Dept, Damanhur, Egypt
[3] Cairo Univ, Natl Canc Inst, Clin Pathol Dept, Cairo, Egypt
来源
INTERNATIONAL JOURNAL OF GENERAL MEDICINE | 2020年 / 13卷
关键词
acute myeloid leukemia; AML; FLT3-ITD; CD34; ACUTE PROMYELOCYTIC LEUKEMIA; FLT3; MUTATIONS; PROGNOSTIC-SIGNIFICANCE; STEM/PROGENITOR CELLS; NPM1; INHIBITION; PREVALENCE; FREQUENCY; CANCER; AML;
D O I
10.2147/IJGM.S276138
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Acute myeloid leukemia (AML) is a common hematological malignancy associated with different cytogenetic and genetic abnormalities. Methods: FLT3-internal tandem duplication (FLT3/ITD) mutation and CD34 expression levels were assessed in the bone marrow (BM) aspirates of 153 de novo AML patients. Data were correlated with relevant clinic-pathological features of the patients, response to treatment, disease-free survival (DFS), and overall free survival (OS) rates. Results: FLT3-ITD mutation was detected in 27/153 (17.6%) AML patients (P=0.001), and CD34 was expressed in 83/153 (54.2%) patients (P=0.293) compared to those with wild FLT3 and CD34(-) expression, respectively. Patients with FLT3-ITD mutation showed increased peripheral blood and BM blast cells, abnormal cytogenetics, poor DFS and OS compared to those with wild FLT3 (P=0.013, P<0.001, P=0.010, P=0.008 and P=0.004, respectively), while there was no significant association with response to treatment (P=0.081). There was no significant association between CD34 expression and response to treatment, DFS, and OS (P>0.05). FLT3-ITD mutation and FAB subtypes were independent prognostic factors for DFS. Older age >= 39 years, HB <7 mg/dL PB blast >= 54%, and FLT3-ITD mutation were independent prognostic factors for poor OS in AML patients. The presence of both FLT3-ITD mutation and CD34 expression associated significantly with resistance to therapy (P=0.024), short DFS and OS rates (P=0.006, P=0.037, respectively). Conclusion: Combined expression of both FLT3-ITD mutation and CD34 expression is an important prognostic and predictive factor for poor disease outcome in AML patients.
引用
收藏
页码:867 / 879
页数:13
相关论文
共 50 条
  • [41] Internal tandem duplication of the FLT3 gene and clinical evaluation in childhood acute myeloid leukemia
    T Iwai
    S Yokota
    M Nakao
    T Okamoto
    M Taniwaki
    N Onodera
    A Watanabe
    A Kikuta
    A Tanaka
    K Asami
    I Sekine
    H Mugishima
    Y Nishimura
    S Koizumi
    Y Horikoshi
    J Mimaya
    S Ohta
    K Nishikawa
    A Iwai
    T Shimokawa
    M Nakayama
    K Kawakami
    T Gushiken
    N Hyakuna
    N Katano
    M Tsurusawa
    T Fujimoto
    Leukemia, 1999, 13 : 38 - 43
  • [42] Improved FLT3 Internal Tandem Duplication PCR Assay Predicts Outcome after Allogeneic Transplant for Acute Myeloid Leukemia
    Grunwald, Michael R.
    Tseng, Li-Hui
    Lin, Ming-Tseh
    Pratz, Keith W.
    Eshleman, James R.
    Levis, Mark J.
    Gocke, Christopher D.
    BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2014, 20 (12) : 1989 - 1995
  • [43] Internal tandem duplication of the FLT3 gene in acute leukemia: Clinical and prognostic implications in acute myeloid leukemia.
    Chi, HS
    Yang, SE
    Choi, SJ
    Park, CJ
    Seo, EJ
    Lee, KH
    BLOOD, 2000, 96 (11) : 104A - 104A
  • [44] Sorafenib monotherapy gives sustainable suppression of FLT3 clone in untreated patients with FLT3-internal tandem duplication positive acute myeloid Leukaemia
    Mohan, Babu P.
    How, Gee-fung
    Loh, Yvonne
    Linn, Yeh-ching
    BRITISH JOURNAL OF HAEMATOLOGY, 2012, 157 (01) : 131 - 132
  • [45] Molecular stratification of patients with normal karyotype acute myeloid leukemia based on initial assessment of FLT3-internal tandem duplication status at first complete remission
    Medeiros, Bruno C.
    Gotlib, Jason
    Zehnder, James
    LEUKEMIA & LYMPHOMA, 2009, 50 (05) : 851 - 853
  • [46] Phase 2 study of azacytidine plus sorafenib in patients with acute myeloid leukemia and FLT-3 internal tandem duplication mutation
    Ravandi, Farhad
    Alattar, Mona Lisa
    Grunwald, Michael R.
    Rudek, Michelle A.
    Rajkhowa, Trivikram
    Richie, Mary Ann
    Pierce, Sherry
    Daver, Naval
    Garcia-Manero, Guillermo
    Faderl, Stefan
    Nazha, Aziz
    Konopleva, Marina
    Borthakur, Gautam
    Burger, Jan
    Kadia, Tapan
    Dellasala, Sara
    Andreeff, Michael
    Cortes, Jorge
    Kantarjian, Hagop
    Levis, Mark
    BLOOD, 2013, 121 (23) : 4655 - 4662
  • [47] CABOZANTINIB IS SELECTIVELY CYTOTOXIC IN ACUTE MYELOID LEUKEMIA CELLS WITH INTERNAL TANDEM DUPLICATION OF FLT3 (FLT3-ITD)
    Wang, A.
    Lu, J. W.
    Hou, H. A.
    Chen, C. Y.
    Hu, C. Y.
    Ou, D. L.
    Ko, Y. C.
    Tien, H. F.
    Lin, L. I.
    HAEMATOLOGICA, 2014, 99 : 291 - 291
  • [48] The size of duplication does not add to the prognostic significance of FLT3 internal tandem duplication in acute myeloid leukemia patients
    Ponziani, V.
    Gianfaldoni, G.
    Mannelli, F.
    Leoni, F.
    Ciolli, S.
    Guglielmelli, P.
    Antonioli, E.
    Longo, G.
    Bosi, A.
    Vannucchi, A. M.
    LEUKEMIA, 2006, 20 (11) : 2074 - 2076
  • [49] The size of duplication does not add to the prognostic significance of FLT3 internal tandem duplication in acute myeloid leukemia patients
    V Ponziani
    G Gianfaldoni
    F Mannelli
    F Leoni
    S Ciolli
    P Guglielmelli
    E Antonioli
    G Longo
    A Bosi
    A M Vannucchi
    Leukemia, 2006, 20 : 2074 - 2076
  • [50] Measurable Residual FLT3 Internal Tandem Duplication Before Allogeneic Transplant for Acute Myeloid Leukemia
    Dillon, Laura W.
    Gui, Gege
    Ravindra, Niveditha
    Andrew, Georgia
    Mukherjee, Devdeep
    Wong, Zoe C.
    Huang, Ying
    Gerhold, Jason
    Holman, Matt
    D'Angelo, Julian
    Miller, Jeffrey
    Higgins, Jake
    Salk, Jesse J.
    Auletta, Jeffery J.
    El Chaer, Firas
    Devine, Steven M.
    Jimenez-Jimenez, Antonio Martin
    De Lima, Marcos J. G.
    Litzow, Mark R.
    Kebriaei, Partow
    Saber, Wael
    Spellman, Stephen R.
    Zeger, Scott L.
    Page, Kristin M.
    Hourigan, Christopher S.
    JAMA ONCOLOGY, 2024, 10 (08) : 1104 - 1110