The landscape of chromosomal aberrations in the tumor cells of the patients with B-ALL is diverse and can influence the outcome of the disease. Molecular karyotyping at the onset of the disease using chromosomal microarray (CMA) is advisable to identify additional molecular factors associated with the prognosis of the disease. Molecular karyotyping data for 36 patients with Ph-negative B-ALL who received therapy according to the ALL-2016 protocol are presented. We analyzed copy number alterations and their prognostic significance for CDKN2A/B, DMRTA, DOCK8, TP53, SMARCA2, PAX5, XPA, FOXE1, HEMGN, USP45, RUNX1, NF1, IGF2BP1, ERG, TMPRSS2, CRLF2, FGFR3, FLNB, IKZF1, RUNX2, ARID1B, CIP2A, PIK3CA, ATM, RB1, BIRC3, MYC, IKZF3, ETV6, ZNF384, PTPRJ, CCL20, PAX3, MTCH2, TCF3, IKZF2, BTG1, BTG2, RAG1, RAG2, ELK3, SH2B3, EP300, MAP2K2, EBI3, MEF2D, MEF2C, CEBPA, and TBLXR1 genes, choosing t(4;11) and t(7;14) as reference events. Of the 36 patients, only 5 (13.8%) had a normal molecular karyotype, and 31 (86.2%) were found to have various molecular karyotype abnormalities—104 deletions, 90 duplications or amplifications, 29 cases of cnLOH and 7 biallelic/homozygous deletions. We found that 11q22-23 duplication involving the BIRC3, ATM and MLL genes was the most adverse prognostic event in the study cohort.

Chromosomal microarray analysis (CMA) was performed for 40 patients with B-ALL undergoing treatment according to the ALL-2016 protocol to investigate the copy number alterations (CNAs) and copy neutral loss of heterozygosity (cnLOH) associated with minimal residual disease (MRD)-positive remission. Aberrations involving over 20,000 genes were identified, and a random forest approach was applied to isolate a subset of genes whose CNAs and cnLOH are significantly associated with poor therapeutic response. We have assembled the triple matched healthy population data and used that data as a reference, but not as a matched control. We identified a recurrent cluster of cnLOH in the 19q13.2–19q13.31 region, significantly enriched in MRD-positive patients (70% vs. 47% in the reference group vs. 16% in MRD-negative patients). This region includes the pregnancy-specific glycoprotein (PSG) gene family and the oncogene ERF, suggesting a potential role in leukemic persistence and treatment resistance. Additionally, we observed significant deletions involving 7p22.3 and 16q13, often as part of large-scale losses affecting almost the entire chromosomes 7 and 16, indicative of global chromosomal instability. These findings highlight specific genomic regions potentially involved in therapy resistance and may contribute to improved risk stratification in B-ALL. Our findings emphasize the value of high-resolution CMA in diagnostics and risk stratification and suggest that PSG genes and other candidate genes could serve as biomarkers for predicting treatment outcomes.

Chromosomal microarray analysis (CMA) detects copy-number alterations and copy-neutral loss of heterozygosity (cnLOH), but the CMA landscape of adult T-ALL has been described in few cohorts. Day +70 measurable residual disease (MRD) is a surrogate marker of early treatment response, available only after induction. Thirty-nine adults with Ph-negative T-ALL on a single protocol underwent diagnostic CMA. Mosaic events were catalogued per chromosome and against a 57-gene panel and described in relation to day +70 MRD status (13 MRD-positive, 25 MRD-negative). The analysis is presented as descriptive without formal inference. Mosaic alterations were present in almost all patients, so groups differed in the amount rather than the presence of genomic change. Complex profiles (≥3 affected chromosomes) were seen in 46.2% of MRD-positive and 20.0% of MRD-negative patients. Biallelic 9p21.3 deletion occurred in both groups, whereas 9p cnLOH without deletion occurred predominantly in MRD-negative patients. Total cnLOH burden did not track with copy-number burden. Copy-number and copy-neutral events are mechanistically distinct and were not interchangeable here: 9p deletion and 9p cnLOH are separable by SNP array and should be reported separately rather than pooled. No association reached significance, although the cohort was too small to detect all but very large effects.

Introduction. The development of therapy resistance and relapses of acute myeloid leukemia (AML), especially in the intermediate prognosis group, may be due to the molecular genetic heterogeneity of tumor cells. Chromosomal microarray analysis (CMA) can detect microdeletions, duplications, and copy-neutral loss of heterozygosity (cnLOH) which may be associated with a response to therapy. Aim: to evaluate tthe frequency of copy number aberrations and cnLOH in leukemogenesis-associated genes in patients with intermediate-stage AML and and their relationship to survival and response to treatment. Materials and methods . The study included 35 patients with de novo AML from the intermediate prognosis group for ELN2017. Copy number analysis by CMA was performed for a panel of 36 genes associated with leukemogenesis. The reference group included 102 healthy individuals without oncohematological disorders who also underwent comparable CMA testing. Results. Genomic aberrations were detected in 91.18 % of patients, most often in the genes of chromatin modifiers (64.7 % patients) and tumor suppressor genes (64.7% patients). The cnLOH type (PHF6, SMC1A, BKORL1) prevailed. KMT2A duplications occurred only in AML patients — 14.3 % (p < 0.001) and were associated with worse survival (log-rank P = 0.05). Combinations of genomic alterations involving 4–7 functional gene groups were found in 20.6% of patients. Conclusion. Driver gene aberrations, especially KMT2A duplications, are associated with an unfavorable clinical outcome in AML with an intermediate prognosis.

Background: The tumor suppressor p53 is a critical regulator of gene expression in cancer, acting through binding to specific p53 response elements (REs). One of key RE rs4590952 is found in the KITLG gene. Aims: This study aimed to precisely investigate the allelic variants of the SNP rs4590952 within patient groups with acute leukemia and to analyze their association with the disease and response to therapy. A specific objective was to determine the frequency and nature of regions of homozygosity encompassing the KITLG locus. Methods: The study cohort included: 37 patients with Ph-negative B-ALL, 38 with T-ALL, and 35 with de novo intermediate-risk AML. A reference group of 200 healthy individuals without oncohematological disorders was used for comparison. Chromosomal microarray analysis (CMA) was performed using the CytoScan™ HT-CMA. Statistical analysis was performed using Python 3.12.4 and SAS 9.4. Results: The allele frequency (AF) of the G allele of rs4590952 was 0.785 in the reference group. Among patients, the AF was 0.833 in T-ALL, 0.757 in B-ALL, and 0.743 in AML. The frequency of copy-neutral loss of heterozygosity (cn-LOH) at 12q21.32, which results in the GG genotype, was significantly higher in the T-ALL group (45%) compared to the reference group (27%) (OR=0.4; 95% CI: 0.2–0.9; p=0.02). A significant association between MRD-positive status and cn-LOH KITLG was found specifically in the T-ALL group (OR=11; 95% CI: 2–62; p=0.005). Cn-LOH KITLG was also significantly associated with poor chemotherapy response in AML (p=0.01). Summary: The GG genotype of the p53 response element in KITLG (rs4590952) frequently arises from acquired cn-LOH at 12q21.32, observed in 45% of T-ALL and 26-27% of other cases. This treatment-response marker, present irrespective of leukemic status, warrants further validation in expanded cohorts.

Immunophenotypic features of plasma cells (pC) in patients with systemic AL‑amyloidosis (AL‑A) are not fully characterized. The bone marrow of 113 patients with first diagnosed systemic AL‑A was studied by 10‑color flow cytofluorimetry. Three densities of differentiation antigen expression were distinguished: negative – less than 10 % of aberrant cells expressed antigen, partial – 10–90 % of cells expressed antigen, positive – more than 90 % of cells expressed antigen. Patients were divided into three groups. Group 1 included 76 patients with AL‑A and a PC count of less than 10 %. The second group consisted of 25 patients with a PC count greater than 10 % but without evidences of symptomatic multiple myeloma. The third group included 12 patients with a PC count greater than 10 % and symptomatic CRAb (AL‑A combined with multiple myeloma). 75 patients received first‑line therapy, including bortezomib, cyclophosphamide, and dexamethasone. When comparing the immunophenotype of aberrant PCs of each individual patient by means of a heat map, no complete match was found in any case, which confirms the uniqueness of clonal PC biology and their high heterogeneity. It was found that aberrant PCs lost expression of CD19 in 95.6 % of cases, CD45 in 78.6 % of patients, CD81 in 37.5 %, and CD27 in 36 %. CD20 was expressed in 7.7 % of patients, CD56 in 48.2 %, and CD117 in 36.8 %. A positive but low (dim) density of CD38 expression was detected in 45 % of patients. There were no statistically significant differences in the expression profile of CD19, CD20, CD27, CD38, CD45, CD56, CD117, CD138, CD200, and CD319 between the patient groups. The frequency of CD269 (bCMA) expression on pC varied depending on the size of the morphologic substrate. Partial expression of Cd269 (bCMA) was detected in 46.7 % of patients in group 1; 84.7 % in group 2 and 100 % in group 3 (p = 0.02). No positive, including high, Cd269 expression, was detected in any AL‑A patient in all three groups. A negative correlation of CD27 expression with the depth of hematologic response on therapy with bortezomib was established: in the absence of CD27 expression, a deep hematologic response was achieved in 87.5 % of cases, and with positive expression of this marker in only 35 % of patients (p = 0.02).