Diagnosis and characterization of acute erythroleukemia subsets by determining the percentages of myeloblasts and proerythroblasts in 69 cases

Kowal-Vern, Areta; Mazzella, Fermina M.; Cotelingam, James D.; Shrit, M. Atef; Rector, James T.; Schumacher, Harold R.

doi:10.1002/1096-8652(200009)65:1<5::aid-ajh2>3.0.co;2-u

Cited by 50 publications

(34 citation statements)

References 24 publications

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“…Lineage identity of cells presenting a positive staining toward p-Akt and p-mTOR was established by double immunolabeling total BMMCs with a myeloid-specific marker, CD33 (30). Furthermore, to evaluate the lineage specificity of the cells, we tested another marker, CD71, which is specific for the erythroid lineage (31). As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

The Akt/Mammalian Target of Rapamycin Signal Transduction Pathway Is Activated in High-Risk Myelodysplastic Syndromes and Influences Cell Survival and Proliferation

Follo¹,

Mongiorgi²,

Bosi

et al. 2007

Cancer Research

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The Akt/mammalian target of rapamycin (mTOR) signaling pathway is important for both cell growth and survival. In particular, an impaired regulation of the Akt/mTOR axis has been strongly implicated in mechanisms related to neoplastic transformation, through enhancement of cell proliferation and survival. Myelodysplastic syndromes (MDS) are a group of heterogeneous hematopoietic stem cell disorders characterized by ineffective hematopoiesis and by a high risk of evolution into acute myelogenous leukemia (AML). The pathogenesis of the MDS evolution into AML is still unclear, although some recent studies indicate that aberrant activation of survival signaling pathways could be involved. In this investigation, done by means of immunofluorescent staining, we report an activation of the Akt/mTOR pathway in high-risk MDS patients. Interestingly, not only mTOR was activated but also its downstream targets, 4E-binding protein 1 and p70 ribosomal S6 kinase. Treatment with the selective mTOR inhibitor, rapamycin, significantly increased apoptotic cell death of CD33 + (but not CD33 À ) cells from high-risk MDS patients. Rapamycin was ineffective in cells from healthy donors or low-risk MDS. Moreover, incubation of high-risk MDS patient CD34 + cells with rapamycin decreased the in vitro clonogenic capability of these cells. In contrast, the phosphoinositide 3-kinase inhibitor, LY294002, did not significantly affect the clonogenic activity of high-risk MDS cells. Taken together, our results indicate that the Akt/mTOR pathway is critical for cell survival and proliferation in high-risk MDS patients. Therefore, this signaling network could become an interesting therapeutic target for treating more advanced MDS cases. [Cancer Res 2007;67(9):4287-94]

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Section: Resultsmentioning

confidence: 99%

The Akt/Mammalian Target of Rapamycin Signal Transduction Pathway Is Activated in High-Risk Myelodysplastic Syndromes and Influences Cell Survival and Proliferation

Follo¹,

Mongiorgi²,

Bosi

et al. 2007

Cancer Research

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“…We acknowledge that the strict WHO definition for PEL helps avoid confusion with other conditions of erythroid hyperproliferation with a left-shifted maturation seen in both non-neoplastic and neoplastic conditions. 4,18 However, if the immature erythroblasts represent a monotonous, overtly neoplastic proliferation, we question the rationale for the requirement of Z80% erythroblasts to qualify a case for PEL as other types of AML (including megakaryocytic) require only Z20% blasts.…”

Section: Discussionmentioning

confidence: 99%

“…[3][4][5][6] In 1992, KowalVern et al 6 proposed including erythroleukemias with Z30% pronormoblasts, the most immature recognizable erythroid precursors, as a subtype of AML. They also proposed modifying the FAB system by renaming FAB-M6 as M6a, and cases that fit with Di Guglielmo disease as M6b.…”

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confidence: 99%

Pure erythroid leukemia: a reassessment of the entity using the 2008 World Health Organization classification

Liu

Hasserjian

et al. 2011

Modern Pathology

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Pure erythroid leukemia (PEL) is rare, characterized by a neoplastic proliferation of erythroblasts. Given recent incorporation of molecular genetic findings and clinical features in the revised 2008 World Health Organization classification scheme of acute myeloid leukemia, we questioned if PEL still remains as a distinct subtype of acute myeloid leukemia. In this retrospective study, we identified 18 cases of acute leukemia with morphologic and immunophenotypic features of PEL. Following the current World Health Organization classification algorithm, these cases were classified as: 13 acute myeloid leukemia with myelodysplasia-related changes, 3 therapy-related acute myeloid leukemia, and 1 chronic myelogenous leukemia blast crisis, and one unclassifiable due to insufficient clinical information. All 16 cases with cytogenetic data harbored an extremely complex karyotype and the median overall survival of the 18 patients was 3 months (range, 1-7 months). This survival was significantly shorter than that of patients with acute erythroid leukemia, erythroid/myeloid subtype, or acute myeloid leukemia with myelodysplasia-related changes with erythroid predominance (Po0.001). PEL is characterized as a neoplastic erythroid hyperproliferation with maturation arrest. E-cadherin emerged as the most sensitive and specific marker for immature erythroblasts, and was helpful in distinguishing PEL from other erythroid proliferations. Our study showed that the criteria for acute myeloid leukemia in the 2008 World Health Organization system facilitate reclassification of PEL cases into other acute myeloid leukemia categories, mainly of acute myeloid leukemia with myelodysplasia-related changes. These new assigned categories fail to capture the distinct features of PEL, where the phenotype of PEL correlates with a very complex karyotype and an extremely aggressive clinical course.

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“…6 There is a male preponderance. 7 The age distribution appears to be bimodal, with a smaller peak below 20 years and a more definitive and broader peak in the seventh decade of life.…”

Section: Clinical Presentationmentioning

confidence: 99%

“…Some authors described three subtypes of AML6: 7 (1) M6A or Di-Guglielmo's syndrome is characterized by greater or equal to 30% of blasts within non-erythroid cells with less than 30% pronormoblasts. This subgroup is related to the evolution of MDS and presents few karyotype abnormalities.…”

Section: Clinical Presentationmentioning

confidence: 99%

Erythroleukemia: a need for a new definition

2002

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The new WHO classification abolishes the frontier between RAEB-t with 20% of blasts and leukemia with 30% of blasts. We review the definitions of erythroleukemia and discuss the relationship between FAB AML6, RAEB-t and AML6 variant. We ask whether secondary erythroleukemias are the same entity as RAEB-t on survival, karyotype and cytologic characteristics. We suggest that 'AML6 variant' with pure erythroid lineage proliferation would be the real de novo erythroleukemia. Current FAB AML6 entity will probably be classified in either subgroup (1) multilineage dysplasia; (2) therapy-related leukemia; or (3) acute erythroid leukemia subdivided into erythroleukemia (erythroid/myeloid) and pure erythroid leukemia, in the WHO classification -a classification which highlights the importance of clinical and cytogenetic prognostic factors.

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Diagnosis and characterization of acute erythroleukemia subsets by determining the percentages of myeloblasts and proerythroblasts in 69 cases

Cited by 50 publications

References 24 publications

The Akt/Mammalian Target of Rapamycin Signal Transduction Pathway Is Activated in High-Risk Myelodysplastic Syndromes and Influences Cell Survival and Proliferation

The Akt/Mammalian Target of Rapamycin Signal Transduction Pathway Is Activated in High-Risk Myelodysplastic Syndromes and Influences Cell Survival and Proliferation

Pure erythroid leukemia: a reassessment of the entity using the 2008 World Health Organization classification

Erythroleukemia: a need for a new definition

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