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Acute Leukemias

Identification of a molecular signature for leukemic promyelocytes and their normal counterparts: focus on DNA repair genes

Leukemia volume 20, pages 1978–1988 (2006)Cite this article

Abstract

Acute promyelocytic leukemia (APL) is a clonal expansion of hematopoietic precursors blocked at the promyelocytic stage. Gene expression profiles of APL cells obtained from 16 patients were compared to eight samples of CD34+-derived normal promyelocytes. Malignant promyelocytes showed widespread changes in transcription in comparison to their normal counterpart and 1020 differentially expressed genes were identified. Discriminating genes include transcriptional regulators (FOS, JUN and HOX genes) and genes involved in cell cycle and DNA repair. The strong upregulation in APL of some transcripts (FLT3, CD33, CD44 and HGF) was also confirmed at protein level. Interestingly, a trend toward a transcriptional repression of genes involved in different DNA repair pathways was found in APL and confirmed by real-time polymerase chain reactor (PCR) in a new set of nine APLs. Our results suggest that both inefficient base excision repair and recombinational repair might play a role in APLs development. To investigate the expression pathways underlying the development of APL occurring as a second malignancy (sAPL), we included in our study eight cases of sAPL. Although both secondary and de novo APL were characterized by a strong homogeneity in expression profiling, we identified a small set of differentially expressed genes that discriminate sAPL from de novo cases.

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Abbreviations

AML:

acute myeloid leukaemia

APL:

acute promyelocytic leukaemia

ATRA:

all-trans retinoic acid

FDR:

false discovery rate

GCOS:

geneChip operating software

GCRMA:

robust multi-array average

HDAC:

histone deacetylase

PCA:

principal component analysis

PML-RARA:

promyelocytic leukemia-retinoic acid receptor alpha

sAML:

AML occurring as a second tumor

sAPL:

APL occurring as a second tumor

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Acknowledgements

We thank Ettore Meccia for valuable and constant support in paper preparation. Research grants: this work was supported by individual grants from AIRC and Ministero della Salute to MB, AIRC and MURST/COFIN to SF.

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Author notes

  1. I Casorelli and E Tenedini: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Environment and Primary Prevention, Section of Experimental Carcinogenesis, Istituto Superiore di Sanità, Rome, Italy

    I Casorelli, M F Blasi, A Giuliani, M Crescenzi & M Bignami

  2. Department of Biomedical Sciences, Section of Biological Chemistry, Università degli Studi di Modena e Reggio Emilia, Modena, Italy

    E Tenedini, E Tagliafico & S Ferrari

  3. Department of Molecular Medicine and Oncology, Istituto Superiore di Sanità, Rome, Italy

    E Pelosi, U Testa & C Peschle

  4. Department of Transfusion Medicine, San Filippo Neri Hospital, Rome, Italy

    L Mele

  5. Cellular Biotechnology and Hematology Department, Università La Sapienza, Rome, Italy

    D Diverio & M Breccia

  6. Department of Biopathology, Università Tor Vergata, Rome, Italy

    F Lo-Coco

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  1. I Casorelli
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Correspondence to M Bignami.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Casorelli, I., Tenedini, E., Tagliafico, E. et al. Identification of a molecular signature for leukemic promyelocytes and their normal counterparts: focus on DNA repair genes. Leukemia 20, 1978–1988 (2006). https://doi.org/10.1038/sj.leu.2404376

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