Dual-color flow cytometric analysis of megakaryocytic DNA ploidy in the investigation of blastic phase chronic myelogenous leukemia with rearrangement of 3q26

Kwong, Yok Lam; Robertson, E. P.; Lee, C. P.; Li, Chan

doi:10.1002/1097-0142(19930615)71:12<3882::aid-cncr2820711215>3.0.co;2-0

Cited by 5 publications

(2 citation statements)

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“…Morphologically mature megakaryocytes represent the largest haematopoietic cells in the bone marrow and are identified by highly lobulated nuclei and abundant cytoplasm (Ellis et al , 1995). Micromegakaryocytes isolated from the 3q21q26 syndrome leukaemias are approximately a third smaller than their normally differentiated counterparts and display a marked dissociation between nuclear and cytoplasmic maturation (Kwong et al , 1993; Kobayashi et al , 1995; Testoni et al , 1999). This morphology might be similar to that displayed in TPA‐induced Evi1‐expressing HEL/FL cells in this study (compare Fig 3A,F with h).…”

Section: Discussionmentioning

confidence: 99%

The Evi1 proto‐oncoprotein blocks endomitosis in megakaryocytes by inhibiting sustained cyclin‐dependent kinase 2 catalytic activity

et al. 2005

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Summary The 3q21q26 syndrome leukaemias are characterised by dystrophic megakaryocytes, elevated platelet counts, ectopic EVI1 protein production and poor prognosis. To investigate the molecular basis of this disease, we developed a model system to examine the biological activity of EVI1 in a megakaryocyte progenitor cell line. For this purpose, Evi1 was conditionally expressed in human erythroleukaemia cells (HEL) that progress along the megakaryocyte lineage in the presence of 12‐O‐tetradecanoylphorbol 13‐acetate (TPA). TPA‐stimulated HEL cells normally undergo: (1) growth arrest; (2) altered morphology; (3) endomitosis and (4) characteristic changes in gene expression, including reduction of the erythroid‐specific glycophoryn A and elevation of the specific glycoproteins GPIIIa and GPVI. Enforced Evi1 expression alone had no effect upon HEL cell proliferation or differentiation but a phenotype was manifest upon stimulation to differentiate. Evi1‐expressing, TPA‐treated HEL cells still showed growth arrest, had reduced and enhanced glycophoryn A and GPIIIa mRNA's, respectively, but failed to significantly elevate GPVI mRNA. This was accompanied by inhibition of endomitosis and altered cell morphology. Sustained CDK2 catalytic activity, typically associated with megakaryocyte endomitosis, was dramatically decreased in TPA‐stimulated Evi1‐expressing HEL cells because of significantly reduced levels of cyclin A. Therefore, enforced Evi1 expression could inhibit megakaryocyte differentiation although retention of some characteristic molecular changes, in combination with a block in endomitosis and altered morphology, suggest a defect in lineage progression. These results suggest that ectopic Evi1 expression contributes to a defective megakaryocyte differentiation programme and is likely to contribute to the phenotype observed in 3q21q26 syndrome leukaemias.

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Section: Discussionmentioning

confidence: 99%

The Evi1 proto‐oncoprotein blocks endomitosis in megakaryocytes by inhibiting sustained cyclin‐dependent kinase 2 catalytic activity

et al. 2005

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“…Megakaryocytic Leukemia (53,74,87) is best recognized by bright expression of platelet glycoproteins CD61 and/or CD41 in a leukemia with relatively little complexity by light scatter. Myeloid antigens CD33 and CD13 are variably expressed, as is CD34, and CD45 can vary from completely negative to brightly positive.…”

Section: Criteria For Diagnosing Particular Diseasesmentioning

confidence: 99%