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


METHODS
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>10-4and sensitivity up to 10-5. This molecular approach enabled the patient's stratification, which was overlooked by classical methods.


CONCLUSIONS
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.
Université de Sousse, faculté de médecine, laboratoire de biochimie, unité de recherche 14 ES 19, 4000 Sousse, Tunisia.
Sawsen
S
Besbes
Université de Sousse, faculté de médecine, laboratoire de biochimie, unité de recherche 14 ES 19, 4000 Sousse, Tunisia.
Walid-Sabri
WS
Hamadou
CHU Pontchaillou, service d'hématologie biologique, 35033 Rennes, France.
Marie-Laure
ML
Boulland
IGH, laboratoire d'immunogénétique moléculaire, 34396 Montpellier, France.
Marie-Paule
MP
Lefranc
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.
Yosra
Y
Ben Youssef
CHU F. Hached, service d'hématologie clinique, 4000 Sousse, Tunisia.
Béchir
B
Achour
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.
Abderrahim
A
Khelif
CHU Pontchaillou, service d'hématologie biologique, 35033 Rennes, France.
Thierry
T
Fest
Université de Sousse, faculté de médecine, laboratoire de biochimie, unité de recherche 14 ES 19, 4000 Sousse, Tunisia. Electronic address: zohra_soua@yahoo.fr.
Zohra
Z
Soua
D017353:Gene Deletion; D005803:Genes, Immunoglobulin; D005819:Genetic Markers; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007147:Immunoglobulin Light Chains / Q000235:genetics*; D060885:Multiplex Polymerase Chain Reaction; D018365:Neoplasm, Residual; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology
D005819:Genetic Markers; C497239:IKZF1 protein, human; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D051740:Ikaros Transcription Factor
B-ALL; Délétion IKZF1; IGH/IGK-Kde rearrangements; IKZF1 deletion; LAL-B; MLPA; MRD; RQ-PCR; Réarrangements IGH/IGK-Kde