Acute promyelocytic leukemia: Immunophenotype and differential diagnosis by flow cytometry

Fang, Hong; Wang, Sa A.; Hu, Shimin; Konoplev, Sergej; Mo, Huan; Liu, Wei; Zuo, Zhuang; Xu, Jie; Jorgensen, Jeffrey L.; Yin, C. Cameron; Hussein, Siba El; Jelloul, Fatima Zahra; Tang, Zhenya; Medeiros, L. Jeffrey; Wang, Wei

doi:10.1002/cyto.b.22085

Cited by 17 publications

(10 citation statements)

References 23 publications

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“…On the other hand, it is known that HLA-DR-negativity is frequently found in non-APL cases of AML [ 62 ]. The expression of CD117, which is also frequently described for APL [ 63 ], was found only in part of the cohort, and in several cases progenitor markers (CD99 and CD34) were also expressed. Partial expression of lysozyme is not typical for APL as well.…”

Section: Discussionmentioning

confidence: 71%

Molecular Heterogeneity of Pediatric AML with Atypical Promyelocytes Accumulation in Children—A Single Center Experience

Borkovskaia

Bogacheva

Konyukhova

et al. 2023

Genes

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Acute promyelocytic leukemia (APL) pathogenesis is based on RARA gene translocations, which are of high importance in the diagnosis of and proper therapy selection for APL. However, in some cases acute myeloid leukemia (AML) demonstrates APL-like morphological features such as atypical promyelocytes accumulation. This type of AML is characterized by the involvement of other RAR family members or completely different genes. In the present study, we used conventional karyotyping, FISH and high-throughput sequencing in a group of 271 de novo AML with atypical promyelocytes accumulation. Of those, 255 cases were shown to carry a typical chromosomal translocation t(15;17)(q24;q21) with PML::RARA chimeric gene formation (94.1%). Other RARA-positive cases exhibited cryptic PML::RARA fusion without t(15;17)(q24;q21) (1.8%, n = 5) and variant t(5;17)(q35;q21) translocation with NPM1::RARA chimeric gene formation (1.5%, n = 4). However, 7 RARA-negative AMLs with atypical promyelocytes accumulation were also discovered. These cases exhibited TBL1XR1::RARB and KMT2A::SEPT6 fusions as well as mutations, e.g., NPM1 insertion and non-recurrent chromosomal aberrations. Our findings demonstrate the genetic diversity of AML with APL-like morphological features, which is of high importance for successful therapy implementation.

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Section: Discussionmentioning

confidence: 71%

Molecular Heterogeneity of Pediatric AML with Atypical Promyelocytes Accumulation in Children—A Single Center Experience

Borkovskaia

Bogacheva

Konyukhova

et al. 2023

Genes

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“…It plays a crucial role in anti-infection immune responses and serves as a key marker of myeloid cell differentiation 46 , 47 . MPO is a vital differentiation marker in diagnosing AML, with its expression levels typically elevated, particularly in AML-M3 46 , 48 . LDLR, a cell-surface glycoprotein, facilitates the endocytosis of cholesterol-rich low-density lipoprotein (LDL) 33 .…”

Section: Discussionmentioning

confidence: 99%

NET-related gene signature for predicting AML prognosis

Wang,

Ding

et al. 2024

Sci Rep

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Acute Myeloid Leukemia (AML) is a malignant blood cancer with a high mortality rate. Neutrophil extracellular traps (NETs) influence various tumor outcomes. However, NET-related genes (NRGs) in AML had not yet received much attention. This study focuses on the role of NRGs in AML and their interaction with the immunological microenvironment. The gene expression and clinical data of patients with AML were downloaded from the TCGA-LAML and GEO cohorts. We identified 148 NRGs through the published article. Univariate Cox regression was used to analyze the association of NRGs with overall survival (OS). The least absolute shrinkage and selection operator were utilized to assess the predictive efficacy of NRGs. Kaplan–Meier plots visualized survival estimates. ROC curves assessed the prognostic value of NRG-based features. A nomogram, integrating clinical information and prognostic scores of patients, was constructed using multivariate logistic regression and Cox proportional hazards regression models. Twenty-seven NRGs were found to significantly impact patient OS. Six NRGs—CFTR, ENO1, PARVB, DDIT4, MPO, LDLR—were notable for their strong predictive ability regarding patient survival. The ROC values for 1-, 3-, and 5-year survival rates were 0.794, 0.781, and 0.911, respectively. In the training set (TCGA-LAML), patients in the high NRG risk group showed a poorer prognosis (p < 0.001), which was validated in two external datasets (GSE71014 and GSE106291). The 6-NRG signature and corresponding nomograms exhibit superior predictive accuracy, offering insights for pre-immune response evaluation and guiding future immuno-oncology treatments and drug selection for AML patients.

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“…The predominant immunophenotypic pattern is seen in APL cases, CD34 and HLA-DR negative blasts, that are positive for CD13, CD33, and CD117 with a bright MPO. Microgranular APL and hypergranular APL are immunophenotypically similar, except for CD34 and CD2, which are more frequently positive in the microgranular variant [ 10 ]. Though several variations may be seen in the APL immunophenotype, MPO positivity is invariable to the point that, when a case of acute leukemia is negative for MPO, the diagnosis of APL is less likely [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

MPO Expression of Background Neutrophils in MPO Negative Acute Promyelocytic Leukemia, An Easy Clue to Corroborate a Challenging Diagnosis: A Case Report and Review of Literature

Krishnamurthy,

Choudhuri,

Ramesh

et al. 2023

Case Reports in Hematology

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Acute promyelocytic leukemia (APL) is characterized by the pathogenic driver fusion transcript PML-RARA resulting from the t(15;17) translocation. Early recognition of APL with prompt ATRA induction has a decisive impact on the early death rate. The preliminary diagnosis of APL relies heavily on cytomorphology and flow cytometry. In APL with variant morphology, such as the microgranular variant, immunophenotype, especially the bright MPO positivity is the basis of diagnosis. Till date, only five cases of APL with reduced/absent MPO have been described in literature. The identification of MPO deficiency based on genetic testing would involve at the least a MPO gene scanning with NGS, followed by microarray to identify somatic uniparental disomy in heterozygotes. This testing is not only redundant given the scant clinical implications of heterozygous MPO deficiency but also time consuming. An easy way to identify background MPO deficiency confounding the immunophenotype of a myeloid neoplasm is the MPO expression in background neutrophils gated on the initial flow cytometry. A dim MPO in the background neutrophils, in the morphological setting of APL, can identify underlying MPO deficiency, clarifying the immunophenotypic ambiguity and thus establishing an unequivocal diagnosis as seen in the current case.

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Acute promyelocytic leukemia: Immunophenotype and differential diagnosis by flow cytometry

Cited by 17 publications

References 23 publications

Molecular Heterogeneity of Pediatric AML with Atypical Promyelocytes Accumulation in Children—A Single Center Experience

Molecular Heterogeneity of Pediatric AML with Atypical Promyelocytes Accumulation in Children—A Single Center Experience

NET-related gene signature for predicting AML prognosis

MPO Expression of Background Neutrophils in MPO Negative Acute Promyelocytic Leukemia, An Easy Clue to Corroborate a Challenging Diagnosis: A Case Report and Review of Literature

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