NPM1-mutated acute myeloid leukemia of monocytic or myeloid origin exhibit distinct immunophenotypes

Liu, Yanrong; Zhu, Hong‐Hu; Ruan, Guo‐Rui; Qin, Ya‐Zhen; Shi, Hong-Xia; Lai, Yue‐Yun; Chang, Yan; Wang, Yazhe; Lü, Dan; Liang, Hao; Li, Jinlan; Li, Ling-Di; Jiang, Bin; Huang, Xiao‐Jun

doi:10.1016/j.leukres.2013.03.009

Cited by 38 publications

(36 citation statements)

References 18 publications

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“…Compared to AML groups with NPM1-wt, the NPM1-mut AMLs were characterized by some peculiar immunophenotypical features, consisting of high CD11b, CD14 and CD116 expression. Our observations are in line with recent studies showing high expression of mature-myeloid cells antigens in NPM1-mut AMLs [30,31].…”

Section: Discussionsupporting

confidence: 93%

miR-21 is overexpressed in NPM1-mutant acute myeloid leukemias

et al. 2015

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Section: Discussionsupporting

confidence: 93%

miR-21 is overexpressed in NPM1-mutant acute myeloid leukemias

et al. 2015

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“…For example, NPM1 mut patients had higher CD33-positive rates and fewer CD34- and HLA-DR-positive rates, whereas CEBPA mutations were associated with high expression of CD34 and CD7. This is the first report to document this observation [28, 29]. Consistent with other studies [30], all four patients with NPM1 mut /FLT3-ITD mut /DNMT3A mut were positive for CD33 and CD13, and negative for surface and cytoplasmic CD3 expression.…”

Section: Discussionsupporting

confidence: 88%

Mutational spectrum and risk stratification of intermediate-risk acute myeloid leukemia patients based on next-generation sequencing

et al. 2016

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Intermediate-risk acute myeloid leukemia (IR-AML), which accounts for a substantial number of AML cases, is highly heterogeneous. Although several mutations have been identified, the heterogeneity of AML is uncertain because novel mutations have yet to be discovered. Here we applied next generation sequencing (NGS) platform to screen mutational hotspots in 410 genes relevant to hematological malignancy. IR-AML samples (N=95) were sequenced by Illumina Hiseq and mutations in 101 genes were identified. Only seven genes (CEBPA, NPM1, DNMT3A, FLT3-ITD, NRAS, IDH2 and WT1) were mutated in more than 10% of patients. Genetic interaction analysis identified several cooperative and exclusive patterns of overlapping mutations. Mutational analysis indicated some correlation between genotype and phenotype. FLT3-ITD mutations were identified as independent factors of poor prognosis, while CEBPA mutations were independent favorable factors. Co-occurrence of FLT3-ITD, NPM1 and DNMT3A mutations was identified with associated with specific clinical AML features and poor outcomes. Furthermore, by integrating multiple mutations in the survival analysis, 95 IR-AML patients could be stratified into three distinct risk groups allowing reductions in IR-AML by one-third. Our study offers deep insights into the molecular pathogenesis and biology of AML and indicated that the prognosis of IR-AML could be further stratified by different mutation combinations which may direct future treatment intervention.

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“…Compared to the previous studies (15,16), which have described the two types of leukemic blasts in NPM1 mutated AML, this study further demonstrates that (1) the myeloid blasts with mutated NPM1 have patternassociated LAIPs that is not significantly altered (except CD34 expression) by treatment status, presence of FLT3 ITD or cytogenetic abnormalities. (2) The leukemic myeloid blasts are present in nearly all of the AML or MDS-EB with mutated NPM1, albeit usually at low-level in acute monocytic leukemia.…”

Section: Discussionsupporting

confidence: 54%

“…Morphologically, AML with mutated NPM1 can have variable myelomonocytic maturation and present as AML with or without maturation, acute myelomonocytic leukemia, or acute monocytic leukemia. The other corresponds to immature monocytes (blast equivalents), that are positive for CD33 and CD64 without significant CD14, CD34, or CD117 (16). Two leukemic immunophenotypes have been described in blasts of AML with mutated NPM1.…”

Section: Introductionmentioning

confidence: 99%

Pattern associated leukemia immunophenotypes and measurable disease detection in acute myeloid leukemia or myelodysplastic syndrome with mutated NPM1

Zhou

Moon

Hoyle

et al. 2018

Cytometry Part B Clinical

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Background: The presence of measurable residual disease after therapy is a significant risk factor of relapse in patients with acute myeloid leukemia (AML). By detecting cells with leukemia-associated immunophenotype (LAIP), multiparameter flow cytometry (MFC) can detect residual leukemia at a level significantly lower than that detected by morphology. However, changes in LAIPs during or after therapy may pose a challenge to MRD testing. AML with mutated NPM1 represents the largest subtype of AML sharing a common leukemogenic mechanism and similar LAIPs. Here, we identified a common pattern of LAIPs in myeloid blasts with mutated NPM1, and studied its stability and limit of detection after therapy.Methods: We summarized aberrancies of leukemic blasts with mutated NPM1 at diagnosis in 61 patients and paired relapse in 25 patients. In addition, we examined the detection of leukemic blasts in 590 specimens collected from 152 patients in complete remission after induction for AML/MDS-EB with mutated NPM1.Results: Our findings demonstrate myeloid blasts with mutated NPM1 have a characteristic pattern of LAIPs that is present in nearly all cases of AML/MDS-EB with mutated NPM1 at initial diagnosis and relapse, regardless of morphologic variations, FLT3 ITD status, or karyotype abnormality. The myeloid blasts with mutated NPM1 can be detected at an approximate level of 0.1% of total leukocytes in morphologic remission with high specificity validated by clinical outcome.Conclusion: The characteristic pattern of LAIPs of myeloid blasts with mutated NPM1 is common and stable, and allows sensitive and specific detection of AML or MDS with mutated NPM1 after therapy.

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NPM1-mutated acute myeloid leukemia of monocytic or myeloid origin exhibit distinct immunophenotypes

Cited by 38 publications

References 18 publications

miR-21 is overexpressed in NPM1-mutant acute myeloid leukemias

miR-21 is overexpressed in NPM1-mutant acute myeloid leukemias

Mutational spectrum and risk stratification of intermediate-risk acute myeloid leukemia patients based on next-generation sequencing

Pattern associated leukemia immunophenotypes and measurable disease detection in acute myeloid leukemia or myelodysplastic syndrome with mutated NPM1

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