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Bull Cancer. 2016 Oct;103(10):822-828. doi: 10.1016/j.bulcan.2016.07.008. Epub 2016 Sep 7.

Combined IKZF1 and IG markers as new tools for diagnosis and minimal residual disease assessment in Tunisian B-ALL.

Author information

1
Université de Sousse, faculté de médecine, laboratoire de biochimie, unité de recherche 14 ES 19, 4000 Sousse, Tunisia.
2
CHU Pontchaillou, service d'hématologie biologique, 35033 Rennes, France.
3
IGH, laboratoire d'immunogénétique moléculaire, 34396 Montpellier, France.
4
Université de Sousse, faculté de médecine, laboratoire de biochimie, unité de recherche 14 ES 19, 4000 Sousse, Tunisia; CHU F. Hached, service d'hématologie clinique, 4000 Sousse, Tunisia.
5
CHU F. Hached, service d'hématologie clinique, 4000 Sousse, Tunisia.
6
Université de Sousse, faculté de médecine, laboratoire de biochimie, unité de recherche 14 ES 19, 4000 Sousse, Tunisia. Electronic address: zohra_soua@yahoo.fr.

Abstract

INTRODUCTION:

The monitoring of minimal residual disease (MRD) approach in patients diagnosed with B-acute lymphoblastic leukemia (B-ALL) allows an early detection of residual clones inducing relapses and therefore appropriate therapy strategy. The molecular markers may identify and quantify the residual blasts in B-ALL with normal cytology. In this study, we aimed to use combined IKZF1, IGH and IGK immunoglobulin genes for diagnosis and MRD monitoring in B-ALL sample using MLPA, multiplex PCR and real-time quantitative PCR.

MATERIAL:

We showed that multiplex PCR and MLPA are necessary and complementary to detect IKZF1 deletions.

RESULTS:

We have identified at the diagnosis clonal IGH rearrangement (VH3-JH5) and IKZF1 deletion (Δ4-7), which we have used it for MRD evaluation after induction chemotherapy. Despite the absence of chromosome abnormality, the patient may be classified in high-risk group with a relapse rate of residual blasts>10-4 and sensitivity up to 10-5. This molecular approach enabled the patient's stratification, which was overlooked by classical methods.

CONCLUSION:

The combined IKZF1 and immunoglobulin genes will be used as appropriate molecular tools for diagnosis and MRD assessment of B-lineage leukemias and introduced as a routine tests in Tunisian clinical laboratories. They will be useful to stratify patients into risk groups leading to better treatment strategy.

KEYWORDS:

B-ALL; Délétion IKZF1; IGH/IGK-Kde rearrangements; IKZF1 deletion; LAL-B; MLPA; MRD; RQ-PCR; Réarrangements IGH/IGK-Kde

PMID:
27614734
DOI:
10.1016/j.bulcan.2016.07.008
[Indexed for MEDLINE]

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