Cytogenetics in the management of clonal chromosomal abnormalities of undetermined significance and persistent polyclonal B-cell lymphocytosis: Guidelines from the Groupe Francophone de Cytogénétique Hématologique (GFCH).

Acquired clonal chromosomal abnormalities (CAs) are usually considered to be disease-related. However, when a CA of this type is the only abnormality present (and especially in small clones), the clinical significance is unclear. Here, we review the literature on recurrent CAs whose significance is regularly subject to debate. Our objective was to help with their interpretation and develop guidelines for sex chromosome loss, trisomy 15, trisomy 8, deletion 20q and other isolated non-myelodysplastic neoplasm (MDS)-defining CAs. We suggest that non-MDS-defining CAs correspond to clonal hematopoiesis of indeterminate potential (CHIP) in the absence of cytopenia and clonal cytopenia of undetermined significance (CCUS) in the presence of cytopenia. Lastly, we review the literature on persistent polyclonal binucleated B-cell lymphocytosis; although usually benign, this condition may correspond to a premalignant state.

The KMT2A recombinome of acute leukemias in 2023.

Chromosomal rearrangements of the human KMT2A/MLL gene are associated with de novo as well as therapy-induced infant, pediatric, and adult acute leukemias. Here, we present the data obtained from 3401 acute leukemia patients that have been analyzed between 2003 and 2022. Genomic breakpoints within the KMT2A gene and the involved translocation partner genes (TPGs) and KMT2A-partial tandem duplications (PTDs) were determined. Including the published data from the literature, a total of 107 in-frame KMT2A gene fusions have been identified so far. Further 16 rearrangements were out-of-frame fusions, 18 patients had no partner gene fused to 5'-KMT2A, two patients had a 5'-KMT2A deletion, and one ETV6::RUNX1 patient had an KMT2A insertion at the breakpoint. The seven most frequent TPGs and PTDs account for more than 90% of all recombinations of the KMT2A, 37 occur recurrently and 63 were identified so far only once. This study provides a comprehensive analysis of the KMT2A recombinome in acute leukemia patients. Besides the scientific gain of information, genomic breakpoint sequences of these patients were used to monitor minimal residual disease (MRD). Thus, this work may be directly translated from the bench to the bedside of patients and meet the clinical needs to improve patient survival.

The complex karyotype in hematological malignancies: a comprehensive overview by the Francophone Group of Hematological Cytogenetics (GFCH).

Karyotype complexity has major prognostic value in many malignancies. There is no consensus on the definition of a complex karyotype, and the prognostic impact of karyotype complexity differs from one disease to another. Due to the importance of the complex karyotype in the prognosis and treatment of several hematological diseases, the Francophone Group of Hematological Cytogenetics (Groupe Francophone de Cytogénétique Hématologique, GFCH) has developed an up-to-date, practical document for helping cytogeneticists to assess complex karyotypes in these hematological disorders. The evaluation of karyotype complexity is challenging, and it would be useful to have a consensus method for counting the number of chromosomal abnormalities (CAs). Although it is not possible to establish a single prognostic threshold for the number of CAs in all malignancies, a specific consensus prognostic cut-off must be defined for each individual disease. In order to standardize current cytogenetic practices and apply a single denomination, we suggest defining a low complex karyotype as having 3 CAs, an intermediate complex karyotype as having 4 CAs, and a highly complex karyotype as having 5 or more CAs.

The MLL recombinome of acute leukemias in 2017.

Chromosomal rearrangements of the human MLL/KMT2A gene are associated with infant, pediatric, adult and therapy-induced acute leukemias. Here we present the data obtained from 2345 acute leukemia patients. Genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and 11 novel TPGs were identified. Thus, a total of 135 different MLL rearrangements have been identified so far, of which 94 TPGs are now characterized at the molecular level. In all, 35 out of these 94 TPGs occur recurrently, but only 9 specific gene fusions account for more than 90% of all illegitimate recombinations of the MLL gene. We observed an age-dependent breakpoint shift with breakpoints localizing within MLL intron 11 associated with acute lymphoblastic leukemia and younger patients, while breakpoints in MLL intron 9 predominate in AML or older patients. The molecular characterization of MLL breakpoints suggests different etiologies in the different age groups and allows the correlation of functional domains of the MLL gene with clinical outcome. This study provides a comprehensive analysis of the MLL recombinome in acute leukemia and demonstrates that the establishment of patient-specific chromosomal fusion sites allows the design of specific PCR primers for minimal residual disease analyses for all patients.

NUP98 is rearranged in 3.8% of pediatric AML forming a clinical and molecular homogenous group with a poor prognosis.

Pediatric acute myeloid leukemia (AML) is a rare disease whose prognosis is highly variable according to factors such as chromosomal abnormalities. Recurrent genomic rearrangements are detected in half of pediatric AML by karyotype. NUcleoPorin 98 (NUP98) gene is rearranged with 31 different fusion partner genes. These rearrangements are frequently undetected by conventional cytogenetics, as the NUP98 gene is located at the end of the chromosome 11 short arm (11p15). By screening a series of 574 pediatric AML, we detected a NUP98 rearrangement in 22 cases (3.8%), a frequency similar to CBFB-MYH11 fusion gene (4.0%). The most frequent NUP98 fusion gene partner is NSD1. These cases are homogeneous regarding their biological and clinical characteristics, and associated with bad prognosis only improved by bone marrow transplantation. We detailed the biological characteristics of these AML by exome sequencing which demonstrated few recurrent mutations (FLT3 ITD, WT1, CEBPA, NBPF14, BCR and ODF1). The analysis of the clonal structure in these cases suggests that the mutation order in the NUP98-rearranged pediatric AML begins with the NUP98 rearrangement leading to epigenetic dysregulations then followed by mutations of critical hematopoietic transcription factors and finally, activation of the FLT3 signaling pathway.

[Acquired and repeated factor VII deficiency during two infectious episodes: a case report]. / Déficit acquis et répété en facteur VII au cours d'épisodes infectieux : à propos d'un cas.

We described the management of a patient with acquired and severe FVII deficiency appeared during two infections outbreaks. This case report focused on both biological diagnosis and treatment of the F VII deficiency.

[Clinical value of the blood measurement of the free light chains of immunoglobulins]. / Intérêt du dosage des chaînes légères libres des immunoglobulines.

Monoclonal free light chains are found in the serum and urine of patients with B-cell proliferative disorders, including multiple myeloma. Measuring free light chains in serum is useful for the diagnosis and monitoring of free light chains diseases. Moreover it could be interesting in the monitoring of treated multiple myeloma with complete immunoglobulin and of monoclonal gammapathy of undetermined significance (MGUS). The goal of our work was to analyze a large cohort of patients with multiple myeloma or MGUS from January 2003 to August 2006 in order to better understand the interest of free light chains.

[Research of 99mTcO4- and 99mTcO2- in injectable solutions of 99mTc-HMDP by inverse phase HPTLC]. / Recherche de 99mTcO4- et de 99mTcO2- dans les solutions injectables de 99mTc-HMDP par HPTLC en phase inverse.

Bone scintigraphy allows the diagnostic of many pathologies related to bone through the intravenous administration of a phosphonate bone marker complexed to 99 metastable technetium (99mTc). The instability of these injectable solutions on contact with air can lead to a mixture of pertechnetate VII (99mTcO4-) and technetium IV (99mTcO2-, xH2O), technetium IV being the only derivative to fix bone. A qualitative control of the purity of these solutions proved to be consequently important before administration. We report here the perfecting of a new chromatographic test based on reverse phase high performance thin layer chromatography (HPTLC). This test, simple, rapid and reproductive allows without ambiguity the detection of 99mTcO4-(VII) and 99mTcO2-(IV), xH2O in hydroxymethylene diphosphonate (HMDP) injectable solutions ready to use.

Intestinal permeability in patients with psoriasis.

A possible relationship between intestinal structure and function in the pathogenesis of psoriasis has recently brought about considerable interest. The purpose of this study was to evaluate the intestinal permeability in psoriatic patients by comparing it with healthy controls. 15 psoriatic patients and 15 healthy volunteers entered the study. Intestinal permeability was evaluated using the 51Cr-labeled EDTA absorption test. The 24-h urine excretion of 51Cr-EDTA from psoriatic patients was 2.46 +/- 0.81%. These results differed significantly from controls (1.95 +/- 0.36%; P less than 0.05). The difference in intestinal permeability between psoriatic patients and controls could be due to alterations in the small intestinal epithelium of psoriatics.

Diagnosis of splenosis: the advantages of splenic scintiscanning with Tc 99m heat-damaged red blood cells.

We present one case of peritoneal splenosis, which was not confirmed by the splenic scintiscan with 99mTc-sulphur colloid, but whose diagnosis, carried out during a second scintiscan with 99mTc-heat-damaged RBC, was confirmed by laparotomy and histology. This case confirms that, for the diagnosis of splenosis, heat-damaged RBC scintigraphy must be used rather than either sulphur colloid scintigraphy or computed-tomography.

[Determination of ventricular volumes by a non-geometric method using gamma-cineangiography]. / Détermination des volumes ventriculaires par une méthode non géométrique utilisant la gamma-cinéangiographie.

The authors suggest a new way of determining ventricular volume by a non-geometric method using gamma-cineangiography. The results obtained by this method were compared with those obtained by a geometric methods and contrast ventriculography in 94 patients. The new non-geometric method supposes that the radioactive tracer is evenly distributed in the cardiovascular system so that blood radioactivity levels can be measured. The ventricular volume is then equal to the ratio of radioactivity in the LV zone to that of 1 ml of blood. Comparison of the radionuclide and angiographic data in the first 60 patients showed systematic values--despite a satisfactory statistical correlation (r = 0.87, y = 0.30 X + 6.3). This underestimation is due to the phenomenon of attenuation related to the depth of the heart in the thoracic cage and to autoabsorption at source, the degree of which depends on the ventricular volume. An empirical method of calculation allows correction for these factors by taking into account absorption in the tissues by relating to body surface area and autoabsorption at source by correcting for the surface of isotopic ventricular projection expressed in pixels. Using the data of this empirical method, the correction formula for radionuclide ventricular volume is obtained by a multiple linear regression: corrected radionuclide volume = K X measured radionuclide volume (Formula: see text). This formula was applied in the following 34 patients. The correlation between the uncorrected and corrected radionuclide volumes and the angiographic volumes was improved (r = 0.65 vs r = 0.94) and the values were more accurate (y = 0.18 X + 26 vs y = 0.96 X + 1.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Factors influencing the quantification of valvular regurgitation by gated equilibrium radionuclide angiography.

To test the clinical validity of the stroke volume ratio (SVR) and the factors influencing its value we determined it in a population of 41 patients free of valvular regurgitation. The SVR was estimated from multigated blood pool scans in left anterior oblique position by two methods. The first method followed the classical formula of the left to right ventricular stroke count ratio. The second method used the same formula except that the right atrial activity emanating from the area of right atrioventricular overlap as traced at right ventricular end-systole, was subtracted from the right ventricular stroke count. The SVR averaged 1.25 +/- 0.18 (range 0.97-1.80) by the first technique and 1.05 +/- 0.12 (range 0.82-1.36) by the second (P less than 0.001). In our results the SVR is not correlated to either ejection fraction or angiographically determined left ventricular volumes. Conversely the SVR is correlated with the left to right end-diastolic volume ratio evaluated from radionuclide counts measured at right and left ventricular end-diastole (r = 0.48, P less than 0.01). This may be due to variations in the area of right atrioventricular overlap, depending on the size of the ventricular chamber. It is postulated that the accuracy of SVR determination could be enhanced by subtraction of the right atrial activity from the right ventricular activity at end-systole. In patients free of valvular regurgitation the LV/RV stroke volume ratio approaches unity and the variability of the results is smaller. Interobserver and intraobserver variability is reduced using the Fourier phase approach.

Temporal Fourier analysis applied to equilibrium radionuclide cineangiography. Importance in the study of global and regional left ventricular wall motion.

Regional and global left ventricular wall motion was assessed in 120 patients using radionuclide cineangiography (RCA) and contrast angiography. Functional imaging procedures based on a temporal Fourier analysis of dynamic image sequences were applied to the study of cardiac contractility. Two images were constructed by taking the phase and amplitude values of the first harmonic in the Fourier transform for each pixel. These two images aided in determining the perimeter of the left ventricle to calculate the global ejection fraction. Regional left ventricular wall motion was studied by analyzing the phase value and by examining the distribution histogram of these values. The accuracy of global ejection fraction calculation was improved by the Fourier technique. This technique increased the sensitivity of RCA for determining segmental abnormalities especially in the left anterior oblique view (LAO).

Preservation of human erythrocytes in the liquid state: biological results with a new medium.

Red blood cells (RBC) were collected with citrate-phosphate-dextrose (CPD) in a blood-pack optimal additive system. After concentration to 90% hematocrit they were diluted with saline-adenine-glucose medium (SAG-RBC), and stored for 35 days. In this work the RBC were stored in the presence of leukocytes. The SAG medium allows RBC conservation during 35 days at +4 degrees C. The adenosine triphosphate (ATP) level of RBC is compatible with their survival. During the first 2 weeks, hemolysis of SAG-RBC was not greater than in CPD blood. Nevertheless, hemolysis reached 1.49% on day 35, and there was a marked increase in RBC osmotic fragility. Scanning electron-microscopic studies of 35-day RBC showed that the majority of them became echinocytes. After incubation in fresh frozen plasma, the RBC recovered satisfactory osmotic resistance and normal disc shape. The post-transfusion viability was normal with greater than 70% recovery after 48 h. The in vivo restoration of 2,3-diphosphoglycerate (2,3-DPG) was rapid in the transfused SAG-RBC, 50% of the initial 2,3-DPG level being restored in 1 h. The in vivo studies proved that the functional quality of these RBC was compatible with their use in transfusion. The most important problem concerns the supernatant hemoglobin level of the SAG-RBC to be used for massive transfusion.