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EVI1 overexpression confers poor prognosis in acute myeloid leukemia (AML). Quantification of EVI1 expression has been mainly assessed by real-time quantitative PCR (RT-qPCR) based on relative quantification of EVI1-1D splice variant. In this study, we developed a RT-qPCR assay to perform quantification of EVI1 expression covering the different splice variants. A sequence localized in EVI1 exons 14 and 15 was cloned into plasmids that were used to establish RT-qPCR standard curves. Threshold values to define EVI1 overexpression were determined using 17 bone marrow (BM) and 31 peripheral blood (PB) control samples and were set at 1% in BM and 0.5% in PB. Samples from 64 AML patients overexpressing EVI1 included in the ALFA-0701 or -0702 trials were collected at diagnosis and during follow-up (n=152). Median EVI1 expression at AML diagnosis was 23.3% in BM and 3.6% in PB. EVI1 expression levels significantly decreased between diagnostic and post-induction samples, with an average variation from 21.6% to 3.56% in BM and from 4.0% to 0.22% in PB, but did not exceed 1 log10 reduction. Our study demonstrates that the magnitude of reduction in EVI1 expression levels between AML diagnosis and follow-up is not sufficient to allow sensitive detection of minimal residual disease.

In core binding factor (CBF) acute myeloid leukaemia (AML), realtime quantitative PCR is useful to quantify the fusion transcript ratio (CBFβ-MYH11 and AML1-ETO, in case of inv(16) and t(8;21) respectively) in peripheral blood and bone marrow during the courses of chemotherapy, in order to monitor minimal residual disease (MRD). In two cases of CBF AML associated with systemic mastocytosis (SM), the persistence of mast cells and the detection of a high ratio of fusion transcript, in bone marrow, during the courses of chemotherapy, led us to determine whether the mast cell component of the disease carried the same molecular alterations as leukaemic blasts. We demonstrate that sorted mast cells carried CBF abnormality. These observations point out the lack of specificity of MRD monitoring by RQ-PCR in these exceptional AML cases with SM. Moreover, this suggests that leukaemic blasts and mast cells derive from a common malignant progenitor.

FLT3 internal tandem duplication (FLT3-ITD) is usually considered as a bad marker for minimal residual disease (MRD) follow-up in acute myeloid leukemia (AML). Our objective was to evaluate the suitability of FLT3-ITD as a target for MRD detection by real-time quantitative PCR, in comparison with two other molecular MRD markers, NPM1 mutation and WT1 overexpression, in 20 adult AML patients treated in Acute Leukemia French Association (ALFA) trials. Overall, these 3 MRD markers showed comparable kinetics in 17/20 (85%) cases. Furthermore, we found that FLT3-ITD MRD levels after induction chemotherapy are predictive of complete remission duration.

Il a ete recemment decrit des mutations du gene GATA2 avec des consequences cliniques variees : lymphœdeme, auto-immunite, deficit immunitaire, cancers (tumeurs solides et hemopathies malignes), affections pulmonaires. Les infections recidivantes notamment a mycobacteries atypiques sont frequemment decrites : syndrome MonoMAC. L’identification de ces mutations permet une prise en charge adaptee ainsi qu’un conseil genetique. Nous rapportons le cas d’un patient de 14 ans hospitalise en novembre 2014 pour prise en charge d’une osteomyelite humerale a Staphylococcus aureus traitee par curetage chirurgical et antibiotherapie par clindamycine et levofloxacine. En fevrier 2015, recidive d’osteomyelite qui avait necessite une nouvelle intervention chirurgicale ainsi qu’une reprise du traitement antibiotique. Plusieurs anomalies etaient decouvertes a l’hemogramme diagnostique (macrocytose VGM 103 μ3, neutropenie 0,8 G/L, monocytopenie 0,1 G/L, thrombopenie 112 G/L). Les myelogrammes successifs montraient une dysmyelopoiese avec un exces de mastocytes. Au caryotype medullaire, il existait un clone avec monosomie 7 : 45, XY, –7. Nous suspections une haplo-insuffisance de GATA2 suite a un 3e episode d’osteomyelite en aout 2015. Un traitement antibiotique anti-mycobacterie atypique d’epreuve de 6 semaines par clarythromycine, rifampicine et moxifloxacine etait instaure et a permis une amelioration clinique. L’analyse en biologie moleculaire confirme une mutation pathogene de GATA2 c.915_916delCT, p.W306AfsX77. Une greffe de moelle osseuse est prevue pour la prise en charge de cette hemopathie constitutionnelle.