Concomitant aberrant overexpression of RUNX1 and NCAM in regenerating bone marrow of myeloid leukemia of Down's syndrome.

Abstract:

BACKGROUND AND OBJECTIVES:Myeloid leukemia of Down's syndrome (ML-DS) has characteristic biological features (e.g. expression of the truncated GATA1s), which are different from those of non-DS childhood acute myeloid leukemias (AML). The objective of this study was to investigate factors predisposing to the development of ML-DS. DESIGN AND METHODS:We analyzed 134 bone marrow specimens from 64 children with ML-DS and non-DS AML during chemotherapy and 7 specimens from DS children with- out leukemia,who did not receive any chemotherapy,The specimens were analyzed by multiparameter flow cytometry and quantitative reverse transcriptase polymerase chain reaction for transcription factors involved in hematopoiesis. RESULTS:Samples taken from children with ML-DS in complete remission during chemotherapy aberrantly expressed CD56 (NCAM) at the surface of monocytic and granulocytic cells. Compared to non-DS AML cases,children with ML-DS had a statistically significant higher proportion of CD56+ cells in the CD33+ fraction: 71%+/-6% vs. 4%+/-1% (p<0.00001). A significant decrease of the amount of CD33+/CD56+ cells was observed during and after maintenance therapy. An increased number of CD33+/CD56+ cells was also present (>85%) in children with DS who did not receive chemotherapy, but showed a left-shift (due to infection), compared with DS children without left-shift (<10% CD33+/CD56+ cells). Within the CD33+/CD56+ fraction, RUNX1 was overexpressed more than 5-fold (p<0.02) compared to CD33+/CD56- cells, whereas there were no differences regarding GATA1, SPI1, ERG or ETS-2 levels. INTERPRETATION AND CONCLUSIONS:The combined overexpression of RUNX1 and NCAM during stress hematopoiesis in children with DS might be a key factor in the development of overt leukemia and/or in the growth advantage of the malignant GATA1s clone in ML- DS.

journal_name

Haematologica

journal_title

Haematologica

authors

Langebrake C,Klusmann JH,Wortmann K,Kolar M,Puhlmann U,Reinhardt D

subject

Has Abstract

pub_date

2006-11-01 00:00:00

pages

1473-80

issue

11

eissn

0390-6078

issn

1592-8721

pii

03906078_10293

journal_volume

91

pub_type

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