Male Karyotype Research Articles

ACCURATE GENOMIC PREDICTION OF MOSAICISM THROUGH CELL DIVISION ORIGIN OF ANEUPLOIDY ANALYSIS IN THE PREIMPLANTATION EMBRYO

Simple intermediate copy number thresholds have proven to provide poor predictive value for diagnosing preimplantation mosaicism (both analytically and clinically). This study aims to validate a method to determine the cell division origin of aneuploidy from a single trophectoderm biopsy, and its ability to accurately predict mosaicism in the remaining embryo. A high throughput and PGT-validated DNA array platform was used to analyze over 800,000 SNPs within trophectoderm biopsies from a subset of PGT cases where parental DNA was available. Mendelian inheritance analyses were performed on embryonic genotypes within aneuploid chromosomes to predict their parental and cell division origins. Positive controls included embryos with a male karyotype (n=279) with known maternal origin of the X chromosome, and unbalanced embryos from PGT-SR cases (n=69) with known meiotic and parental origins of aneuploidy. The method was applied to clinical biopsies with aneuploidy and compared to rebiopsies (n=80) to evaluate the accuracy of predicting mosaicism (mitotic) and uniform (meiotic) aneuploidy. All samples were analyzed while blinded to prior results. Following validation, the incidence of mitotic origin of aneuploidy was investigated in 942 embryos. Blinded predictions of the X chromosome origin in male embryos, and parental and cell division origin of aneuploidy in PGT-SR derived unbalanced embryos were 100% concordant with expected results, demonstrating the validity of predicting parental and meiotic cell division origins of aneuploidy. Blinded analysis of rebiopsies showed that all embryos with mitotic origin of aneuploidy predicted in the original biopsy were confirmed as mosaic, and all embryos with meiotic origin were confirmed as uniform aneuploid, demonstrating the validity of predicting mitotic origins of aneuploidy and mosaicism. The overall incidence of mitotic whole chromosome aneuploidy (mosaicism) in embryos was 3%. The overall embryonic aneuploidy rate was 31% (mean maternal age 34.5+4). Aneuploid chromosomes primarily originated from the maternal genome (80%) and maternal whole chromosome aneuploidy primarily originated from meiotic errors (95%), while paternal aneuploidy more often originated from mitotic errors (35%)(p<0.05). These data indicate very high specificity in predicting mosaicism from a single aneuploid trophectoderm biopsy and a low prevalence of mosaicism (3%) in the human blastocyst. This is in stark contrast to existing methods of predicting mosaicism with intermediate copy number thresholds, where rebiopsy confirmation rates are ∼40%, and prevalence is estimated to be ∼20%. Improving the specificity of predicting mosaicism (reducing false positives) from a single biopsy may provide a unique opportunity to investigate the true clinical consequence of transferring bona fide mosaic embryos for the first time.

Molecular study and genotype–phenotype in Chinese female patients with 46, XY disorders of sex development

Objective The rare condition 46, XY disorders of sex development (DSDs) is characterized by the female phenotype and male karyotype. We aimed to describe the genetic basis of 46, XY DSDs in nine patients and the genotype–phenotype relationships of the genes involved. Methods Targeted next-generation sequencing (NGS) was used to analyze the underlying hereditary etiology in nine female patients with 46, XY DSDs. In silico analyses were used to predict the effects of novel variants on the protein function of the identified genes. Results Primary amenorrhea with the absence of puberty, inguinal hernia, and clitoridauxe were common complaints. All enrolled patients had a differential etiology by genetic testing, and five novel genetic variants involved in four genes (SRY, AR, NR5A1, and LHCGR) were identified. A novel nonsense variant of SRY c.51C > G was found in XY patients without testicles. Two novel heterozygous variants, i.e. c.265A > T (Ile89Leu) and c.422T > C (Val141Ala), of the LHCGR gene were found in male pseudo-hermaphroditism. Conclusions We expanded the genetic mutation spectrum and described in detail the genotype–phenotype relationships of 46, XY DSDs. DNA sequencing for SRY should be a priority in female patients with 46, XY DSDs. NGS is useful for clarifying genetic pathogenesis and could provide a basis for clinical diagnosis and treatments of patients with 46, XY DSDs.

Generation and characterization of human induced pluripotent stem cell line METUi001-A from a 25-year-old male patient with relapsing-remitting multiple sclerosis

Multiple sclerosis is a chronic disease characterized by inflammation, demyelination, and axonal damage in the central nervous system. Here, we established an induced pluripotent stem cell (iPSC) line METUi001-A from the peripheral blood mononuclear cells of a 25-year-old male individual with clinically diagnosed Relapsing-Remitting Multiple Sclerosis (RRMS) using the integration-free Sendai reprogramming method. We demonstrated that the iPSCs are free of exogenous Sendai reprogramming vectors, have a normal male karyotype, express pluripotency markers, and differentiate into the three germ layers. The iPSC line can serve as a valuable resource to generate cellular model systems to investigate molecular mechanisms underlying RRMS.

Cloning and physical localization of male-biased repetitive DNA sequences in Spinacia oleracea (Amaranthaceae)

Spinach (Spinacia oleracea Linnaeus, 1753) is an ideal material for studying molecular mechanisms of early-stage sex chromosome evolution in dioecious plants. Degenerate oligonucleotide-primed polymerase chain reaction (DOP-PCR) technique facilitates the retrotransposon-relevant studies by enriching specific repetitive DNA sequences from a micro-dissected single chromosome. We conducted genomic subtractive hybridization to screen sex-biased DNA sequences by using the DOP-PCR amplification products of micro-dissected spinach Y chromosome. The screening yielded 55 male-biased DNA sequences with 30 576 bp in length, of which, 32 DNA sequences (12 049 bp) contained repeat DNA sequences, including LTR/Copia, LTR/Gypsy, simple repeats, and DNA/CMC-EnSpm. Among these repetitive DNA sequences, four DNA sequences that contained a fragment of Ty3-gypsy retrotransposons (SP73, SP75, SP76, and SP77) were selected as fluorescence probes to hybridization on male and female spinach karyotypes. Fluorescence in situ hybridization (FISH) signals of SP73 and SP75 were captured mostly on the centromeres and their surrounding area for each homolog. Hybridization signals primarily appeared near the putative centromeres for each homologous chromosome pair by using SP76 and SP77 probes for FISH, and sporadic signals existed on the long arms. Results can be served as a basis to study the function of repetitive DNA sequences in sex chromosome evolution in spinach.

Cloning and physical localization of male-biased repetitive DNA sequences in Spinacia oleracea (Amaranthaceae).

Spinach (Spinacia oleracea Linnaeus, 1753) is an ideal material for studying molecular mechanisms of early-stage sex chromosome evolution in dioecious plants. Degenerate oligonucleotide-primed polymerase chain reaction (DOP-PCR) technique facilitates the retrotransposon-relevant studies by enriching specific repetitive DNA sequences from a micro-dissected single chromosome. We conducted genomic subtractive hybridization to screen sex-biased DNA sequences by using the DOP-PCR amplification products of micro-dissected spinach Y chromosome. The screening yielded 55 male-biased DNA sequences with 30 576 bp in length, of which, 32 DNA sequences (12 049 bp) contained repeat DNA sequences, including LTR/Copia, LTR/Gypsy, simple repeats, and DNA/CMC-EnSpm. Among these repetitive DNA sequences, four DNA sequences that contained a fragment of Ty3-gypsy retrotransposons (SP73, SP75, SP76, and SP77) were selected as fluorescence probes to hybridization on male and female spinach karyotypes. Fluorescence in situ hybridization (FISH) signals of SP73 and SP75 were captured mostly on the centromeres and their surrounding area for each homolog. Hybridization signals primarily appeared near the putative centromeres for each homologous chromosome pair by using SP76 and SP77 probes for FISH, and sporadic signals existed on the long arms. Results can be served as a basis to study the function of repetitive DNA sequences in sex chromosome evolution in spinach.

An iPS cell line SDUBMSi0011-A from a multiple epiphyseal dysplasia patient carrying c. 1076T > G mutation in the SMOC2 gene

SMOC2 gene encodes a modular extracellular protein and its mutation causes multiple epiphyseal dysplasia (MED) which characterized by short stature and osteoarthritis. Here, we generated an induced pluripotent stem cell line from a MED patient with c. 1076T > G transition mutation in SMOC2 gene. The iPSCs line has a normal male karyotype and the same mutation as the MED patient. It also expresses pluripotent markers and can differentiate into the three germ layers.

Disorder of Sexual Development Males With XYY in Blood Have Exactly X/XY/XYY Mosaicism in Gonad Tissues.

Y chromosome represents masculinization. The extra Y chromosome of XYY patients usually leads to over-masculinization phenotypes. The occurrence of several DSD cases with XYY in blood is controversial. Is XYY associated with disorder of sex development (DSD)? What is the mechanism behind DSD in males with XYY in blood? To this end, this study retrospectively analyzed blood-karyotype data of 4,437 DSD male children and karyotypes data of 6,259 newborn males as the control. Exome sequencing (ES) was performed to test whether the patients with DSD and with XYY in blood had other variants on known DSD-genes. Testicular biopsy was performed. Fluorescence in situ hybridization (FISH) was used to test whether a sex chromosome mosaicism was present in the oral epithelial cells or gonad tissue of patients with DSD and with XYY in blood. Among 4,437 DSD males who received cytogenetic evaluation, 14 patients with 47,XYY were identified. By contrast, five individuals among the 6,259 controls had 47,XYY. XYY in blood is more frequent among males with DSD than in other males (p = 0.004). The XYY karyotypes were confirmed again by GTG-banding in blood samples and by FISH performed on oral epithelial cells. ES on seven XYY DSD patients was successfully performed, but results did not identify any pathogenic variant on 55 known DSD genes. Gonad biopsy (n = 3) revealed testicular dysplasia and true hermaphroditism. FISH of gonad tissues (n = 3) showed that all of the samples had mosaic for X/XY/XYY. This study is the first to investigate the relationship between XYY in blood and DSD. The knowledge that XYY is in the blood and in oral cells have X/XY/XYY mosaicism in gonadal tissue is new for both researchers and clinicians who seek to understand the genetic basis of DSD males.

Establishment of PLAFMCi004-A induced pluripotent stem cells derived from PBMCs from a healthy individual

Peripheral blood mononuclear cells (PBMCs) were isolated from a healthy male individual. PBMCs were reprogrammed into human induced pluripotent stem cells (iPSCs) using plasmids carrying the following reprogramming factors: NANOG, LIN28, OCT4, SOX2, c-MYC, and KLF4. This cell line expressed pluripotency markers, exhibited the normal male karyotype (46, XY), and had the potential to differentiate into 3 germ layers, as confirmed by techniques such as flow cytometry. The iPSC obtained from a healthy individual can be used for organoids to reveal developmental mechanism of tissue and organ regeneration, stem cell therapy and drug screening.

Generation of a hiPSC line ZZUNEUi017-A from a patient with dilated cardiomyopathy caused by mutation in TTN.

Dilated cardiomyopathy (DCM) is the commonest type of cardiomyopathy. In this study, peripheral blood mononuclear cells (PBMCs) were isolated from a DCM patient with the p. Glu12513fs(c.37537delG) mutation in TTN and were reprogrammed to human induced pluripotent stem cells (iPSCs). The ZZUNEUi017-A iPSC line expressed pluripotency markers, exhibiting a normal male karyotype (46, XY) and demonstrating differentiation potential into three germ layers in vitro.

Classical and molecular cytogenetics of Belontia hasselti (Perciformes: Osphronemidae): Insights into the ZZ/ZW sex chromosome system

Abstract. Chaiyasan P, Mingkwan B, Jantarat S, Suwannapoom C, Cioffi MDB, Liehr T, Talumphai S, Tanomtong A, Supiwong W. 2021. Classical and molecular cytogenetics of Belontia hasselti (Perciformes: Osphronemidae): Insights into the ZZ/ZW sex chromosome system. Biodiversitas 22: 546-554. Karyotype of Java combtail fish, Belontia hasselti, from To Daeng peat swamp forest, Narathiwat Province, southern Thailand, was studied for the first time. Mitotic chromosome preparations were prepared directly from kidney cells from ten male and ten female fish. Conventional staining, NOR banding, and molecular cytogenetics with fluorescence in situ hybridization (FISH) using 5S and 18S rDNAs, as well as microsatellites d(CA)15 and d(CAC)10 as probes were applied. The diploid chromosome number (2n) was 48 and a female heterogametic sex chromosome system (ZZ/ZW) is suggested. The fundamental numbers (NF) were 48 and 49 in males and females, respectively. The karyotype of males comprised 48 telocentric chromosomes while the female ones were composed of one metacentric and 47 telocentric chromosomes. A single Ag-NOR-bearing chromosomal pair was identified. The NOR positions were characterized at the interstitial sub-centromeric region of pair 13, which coincided with signals of 18S rDNA and d(CAC)10 probes. The 5S rDNA signals were located at interstitial sites of the largest telocentric pair. Microsatellite d(CA)15 repeats were highly distributed throughout almost all entire chromosomes except for centromeric regions on some chromosome pairs, including sex chromosomes. The present study is a novel report for a ZZ/ZW sex chromosome system of this fish family in Thailand.

Establishment of patient-specific induced pluripotent stem cell line SDUBMSi009-A from a patient with X-linked Lowe syndrome.

X-linked Lowe syndrome is a multisystem disorder showing major abnormalities in the eyes, kidneys and central nervous system. OCRL gene, which encodes an inositol polyphosphate 5-phosphatase, is associated with Lowe syndrome when mutated. Here we report the establishment of SDUBMSi009-A, an induced pluripotent stem cell line derived from patient carrying splicing variant (c. 940-11G>A) of OCRL gene by non-integrative reprogramming technology. The iPSC line showed strong pluripotent characteristics, including expressing pluripotent markers and potential to differentiate into the three germ layers. In the meanwhile, the iPSC line kept a normal male karyotype.

Cytogenetic Study of Patients with Primary Amenorrhea in the Northeast of Iran.

Background & Objective:Primary amenorrhea refers to the absence of menstruation in females of reproductive by age 16 when the development of secondary sexual characteristics is evident (breast development, pubic hair) or by age 14 when there are no secondary sexual characteristics are present. Primary amenorrhea can occur in several quite different reasons. Common hormonal causes of primary amenorrhea include constitutional delay, hypothalamic or pituitary disorders, chronic systemic disease, and primary ovarian insufficiency, some endocrine gland disorders, and other causes. Previous studies suggested that chromosomal abnormality is the second most common cause of amenorrhea. This report aims to measure the prevalence of the chromosomal abnormality in primary amenorrhea (PA) patients in the northeast of Iran.Methods:Chromosomal study was carried out on 200 patients with clinical features. The standard method for culturing peripheral venous blood lymphocyte was to prepare metaphase chromosomes and perform routine GTG band analysis.Results:The results revealed that 71% of PA had normal female karyotype (46,XX) and 29% showed different chromosomal abnormalities. The chromosomal abnormalities can be categorized into seven primary groups with or without mosaicism. 1- The most common karyotype was X chromosome aneuploidy (10.5%, n=21), 2- Male karyotype with or without structural abnormality of Y chromosome (5.5 %, n=11), 3- Mosaicism of turner karyotype and structural anomalies of X chromosome (4%, n=8), 4- Structural anomalies of the X chromosome (3.5%, n=7), 5- Mosaicism of turner karyotype and normal karyotype (3%, n=6), 6- Mosaicism of turner karyotype and male karyotype (1.5%, n=3) and 7- Super female karyotype (1%, n=2).Conclusion:The present study has emphasized that early cytogenetic and timely investigation can be necessary for the evaluation of primary amenorrhea.

Behaviour, feeding and cytogenetic features of the wingless blood-sucking ectoparasite Cyanolicimex patagonicus (Heteroptera: Cimicidae).

Cyanolicimex (Haematosiphoninae) includes a single species, C. patagonicus, which is found in the largest known colony of its avian host Cyanoliseus patagonus (Psittacidae) located in Patagonia (Argentina). Relationships between Cyanolicimex and other genera of Haematosiphoninae are still unclear because this genus shares some characters with other South American genera and possesses some similarities with Hesperocimex from the Neoarctic region. The aim of the present study was to provide additional data of C. patagonicus so as to better understand its relationships with other South American species. We examined some biological features of C. patagonicus in the field and we performed a cytogenetic analysis. We observed in the field that C. patagonicus does not live inside the hollow nests of Cyanoliseus patagonus. The cytogenetic analysis showed that the male karyotype is 2n= 31= 28A+X1X2Y and revealed an achiasmate male meiosis and of the collochore type. Our results together with available cytogenetic data in other cimicids, allow proposing the possible chromosomal rearrangements involved in the chromosomal evolution of C. patagonicus and also contribute to better understand the evolutionary divergence at the chromosomal level within Haematosiphoninae. Based on the whole evidence, we propose to place in four groups the species of Haematosiphoninae cytogenetically hitherto studied.

A clinical case of partial androgen resistance syndrome (Reifenstein syndrome)

In the paper we describe a clinical case and provide integrated clinical and laboratory data of a patient with partial androgen resistance syndrome. A 25-year-old male was referred for medical evaluation for an infertile marriage. After a comprehensive assessment, he was diagnosed with hypergonadotropic hypogonadism, coronal hypospadia, left-sided varicocele, and oligoasthenoteratozoospermia. Cytogenetic analysis showed normal male karyotype (46,XY). Molecular genetic analysis identified the c.731_736delCGGTGT mutation in the exon 1 of the androgen receptor (AR) gene, what allowed for making a diagnosis of Reifenstein syndrome. In addition, we give a brief literature review of the clinical conditions associated with abnormal androgen sensitivity and discuss the problems of testing and counseling of patients with partial androgen resistance syndrome.

Generation of an induced pluripotential stem cell (iPSC) line from a patient with hypertrophic cardiomyopathy carrying myosin binding protein C (MYBPC3) c.3369-3370 insC mutation.

Hypertrophic cardiomyopathy (HCM) is a disease in which the heart muscle becomes abnormally thick making it difficult for the heart to pump blood. In this study an induced pluripotent stem cells (iPSC) line was derived from peripheral blood mononuclear cells of a 62-year-old male hypertrophic cardiomyopathy (HCM) patient with the mutation of heterozygous pathogenic myosin binding protein C (MYBPC3) c.3369-3370 insC using an episomal method. The generated iPSC line presented normal 46, XY male karyotypes, expressed pluripotent markers and could spontaneously differentiate into triblast cells. This HCM-specific iPSC line could act as a useful tool for studying and modeling hypertrophic cardiomyopathy.

Generation of an induced pluripotent stem cell line SMBCi010-A from a male with Multiple Osteochondroma carrying a EXT1 mutation.

Multiple Osteochondroma is an abnormal skeleton development autosomal dominant genetic disease which caused by the mutation of EXT1 gene. In this study, we generated induced pluripotent stem cells (iPSCs) from the mesenchymal stem cells (MSCs) of a 12-year-old male patient by reprogramming MSCs with non-integrative vectors. The iPSCs line expresses pluripotent markers, has a normal male karyotype and can differentiate into the three germ layers.

Case about Swyer syndrome (complete, or “pure” gonadal dysgenesis)

46XY - Swyer syndrome (complete, or “pure” gonadal dysgenesis) can be briefly described as a female phenotype in the male genotype. The disease is named for the British endocrinologist Gerald Swyer, who described it in 1955. The full form of dysgenesis is nonsyndromic (not accompanied by extragenital malformations), excludes the duality of sexual development (the presence of male primary sexual characteristics along with female ones), psychological development occurs according to the female type. Congenital pathology occurs in one case in 180,000 individuals with a male karyotype and is recorded more often than other forms of XY-dysgenesis of gonads. Based on these results of the one female, the diagnosis of Swiera syndrome (complete genital dysgenesis: impaired sexual development) was suspected.

Case about Swyer syndrome (complete, or “pure” gonadal dysgenesis)

46XY - Swyer syndrome (complete, or “pure” gonadal dysgenesis) can be briefly described as a female phenotype in the male genotype. The disease is named for the British endocrinologist Gerald Swyer, who described it in 1955. The full form of dysgenesis is nonsyndromic (not accompanied by extragenital malformations), excludes the duality of sexual development (the presence of male primary sexual characteristics along with female ones), psychological development occurs according to the female type. Congenital pathology occurs in one case in 180,000 individuals with a male karyotype and is recorded more often than other forms of XY-dysgenesis of gonads. Based on these results of the one female, the diagnosis of Swiera syndrome (complete genital dysgenesis: impaired sexual development) was suspected.

Acquired Amegakaryocytic Thrombocytopenic Purpura Associated with a Paroxysmal Nocturnal Hemoglobinuria Clone: A Case Report and Review of the Literature

Background: Acquired amegakaryocytic thrombocytopenic purpura (AATP) is a rare bone marrow disorder characterized by a marked reduction in megakaryocytes with otherwise normal hematopoiesis. Both humoral and cell-mediated suppression of megakaryocytopoeisis have been postulated as mechanisms causing AATP. Herein we report a case of a 67-year-old man diagnosed with AATP with a co-existent paroxysmal nocturnal hemoglobinuria (PNH) clone and review the literature on AATP, focusing on proposed etiologies for this rare condition. Case: A 67-year-old man presented to clinic with a 1-week history easy bruising, petechiae and a platelet count of 6 x 109/L. He had a history of left elbow bursitis caused by S. pyogenes, treated with antibiotics 6-months prior to his presentation. His CBC was normal at that time. On assessment, HIV, HBV, HCV, and H. pylori serologies were negative; CMV and EBV serologies were positive for IgG and negative for IgM. ANA and RF were negative, and vitamin B12 level was normal. There was no hepatosplenomegaly on ultrasound. Bone marrow aspirate and biopsy demonstrated a normocellular marrow with severe megakaryocytic hypoplasia. Cytogenetics demonstrated normal male karyotype with loss of Y chromosome in 9/20 metaphases. Flow cytometry revealed a population of 3.99% GPI-deficient neutrophils by FLAER assay. Molecular testing for myeloid mutations and T-cell gene rearrangement is pending. The patient was initially treated with corticosteroids and IVIG, and showed no response with persistent isolated thrombocytopenia. He was managed with platelet transfusions which resulted in a normal platelet increment of 35 x 109/L 1-hour post-transfusion. A diagnosis of AATP was established and he was admitted for immunosuppressive therapy (IST) with ATG and cyclosporine. Methods: We conducted a narrative review of the literature on AATP, searching MEDLINE and EMBASE for articles on AATP published in English between 1946 and 2020. Reference lists of selected articles were reviewed to identify additional cases. We extracted data on presentation, bone marrow findings (including cytogenetics, molecular genetics, and flow cytometry), treatment regimens and outcomes. Results: We identified 47 cases of adult patients with thrombocytopenia attributed to AATP reported in the literature (Table 1). Three main mechanisms were proposed: (i) cell-mediated autoimmunity, (ii) humoral autoimmunity, and (iii) intrinsic stem cell defect. All three mechanisms were supported by in vitro studies, which demonstrated suppression of colony forming unit-megakaryocytes (CFU-M) by patients' T-lymphocytes (Gerwitz et al. 1986; Colovic et al. 2004) and serum (Hoffman et al. 1982) found to contain IgG antibodies inhibiting CFU-M formation, as well as intrinsic defects in CFU-M progenitor proliferation. Few studies reported cytogenetic abnormalities and only one documented molecular genetic testing. Response to IST was reported in several cases, most commonly ATG and cyclosporine. Four recent cases demonstrated remission following treatment with TPO agonists eltrombopag and romiplostim. Six cases progressed to aplastic anemia and 4 to myelodysplastic syndrome (MDS). Flow cytometry results were not reported in the majority of cases, and only 1 case reported coexistence of a PNH clone, identified in a pregnant patient with AATP (Zimmerman et al. 2019). Discussion: AATP is defined as severe thrombocytopenia with bone marrow showing marked decrease or absence of megakaryocytes with preservation of other cell lineages. This broad definition encompasses a range of causes, and our review of the literature highlights the heterogenous nature of AATP which has several proposed mechanisms and a number of therapeutic options. The best evidence suggests that AATP is often secondary to T-cell-mediated suppression of megakaryocytopoeisis, which has been demonstrated by in vitro studies, and is supported in vivo by a case of AATP following PD-1 inhibition (Iyama et al. 2020), and frequent response of AATP to T-cell-directed IST. The co-existence of a PNH clone in our case lends further support to a T-cell-mediated autoimmune process, analogous to the mechanism described in aplastic anemia and hypoproliferative MDS. The application of molecular diagnostics may help to further elucidate the role of clonal hematopoiesis and intrinsic stem cell defects versus humoral and cell-mediated autoimmunity in AATP. Disclosures No relevant conflicts of interest to declare.

Hypodiploidy in patients with acute lymphoblastic leukemia

Background. Acute lymphoblastic leukemia (ALL) is characterized by different clinical course and different sensitivity to therapy. Taking into consideration their significant prevalence an intensive search for new prognostic criteria is conducted that may determine individual prognosis and choose the most appropriate treatment approach for patients with ALL, who often require transfusion therapy and replacement therapy with blood components.&#x0D; Objective. To detect the frequency, diagnostic and prognostic significance of hypodiploidy in patients with ALL.&#x0D; Materials and methods. Standard cytogenetic investigation of bone marrow and/or peripheral bloodcells was performed according to the standard techniques from 57 adult patients with ALL.&#x0D; Results and discussion. Chromosomal aberrations of various kinds were found in 37 (65 %) patients with ALL. Among them presence of one karyotype abnormality was established in 9 (24 %) patients, two abnormalities – in 10 (27 %) and multiple structural and/or numerical changes (≥3) – in 18 (49 %). Samples from 20 (35 %) patients showed a normal female or male karyotype without cytogenetically visible changes. The most common abnormalities in ALL were: trisomy 8, rearrangements of 7q, 17p and 11q23, translocations t(4;11)(q21;q23), t(9;22)(q34;q11), marker chromosomes, acentric structures, hypodiploidy, hyperdiploidy, complex karyotype (≥3 changes) etc. Hypodiploidy was found in 2 (4 %) patients with ALL. One patient, except for abnormal ones, had normal metaphases in him karyotype. Of two patients with hypodiploidy, one had only numerical abnormalities, whereas other one had also structural cytogenetic aberrations, except the numerical changes, namely t(1;6)(q32;q27), add(12)(q24), del(17)(p11), r(17)(p13q25). Hypodiploidy is an unfavorable marker in ALL and a near haploidy is an extremely unfavorable factor.&#x0D; Conclusions. Cytogenetic abnormalities of various kinds were found in 37 (65 %) patients with ALL. The frequency of hypodiploidy was 4 %. ALL patients with hypodiploidy were classified into cytogenetic categories of ALL with a poor risk prognosis. Thus, cytogenetic investigations should be included in the standard examination of patients with ALL for diagnosis, prognosis and selection the optimal treatment strategy.