Chromosome Studies Research Articles

Protocolo diagnóstico endocrinológico de la infertilidad

Infertility affects approximately 15% to 20% of couples. Factors can include both females and males as well as mixed factors and its causes may be idiopathic or unknown. The main causes of female infertility include ovulatory dysfunctions; uterine or cervical abnormalities; fallopian tube problems; and endocrinological causes such as polycystic ovary syndrome, hyperprolactinemia, hypothyroidism, hyperthyroidism, and obesity. The evaluation begins with a complete medical history and physical examination followed by tests to assess ovulatory function as well as a biochemical and hormonal analysis. Male infertility, which affects a significant proportion of couples, may be caused by testicular dysfunction, endocrinopathies, lifestyle factors, congenital anatomical anomalies, exposure to gonadotoxic drugs, and aging. The evaluation includes a detailed medical history and complete physical examination followed by semen analysis to assess sperm concentration, motility, and morphology. Imaging tests and molecular and chromosomal studies are also performed in specific cases.In both sexes, a biochemical and hormonal evaluation is crucial to identify possible endocrinological causes of infertility. Levels of hormones such as FSH, LH, testosterone, and prolactin must be measured to determine gonadal function and detect possible underlying hormonal disorders. The interpretation of these results helps guide the diagnosis and treatment of infertility.

Chromosome Study of Six Populations of Trifolium tumens Stev. ex M. B. in IRAN

Trifolium tumens Stev. ex M. B is a perennial legume with long‐lived and deep rooting from the Vesicaria section in Trifolium genus. It is distributed in Iran. The base chromosome number (x = 8) in the population, confirmed the views of the previous researchers. In this study, the number of chromosomes in the mitotic metaphase stage in the meristematic cells of the root ends were counted in six populations of Trifolium tumens. Also, chloroplast count of stomata guard cells, morphological studies, pollen grain size and flowcytometry were studied in six accessions. Our results showed that this species has ploidy level (2n=16, 2n=32). and the tetraploid state in the species T. tumens is reported. Through flowcytometry, chloroplast count of stomata guard cells and compare the pollen grain, different characters were showed between diploid and tetraploid populations, too. Based on the results, this new cytotype is reported from Iran.

Improving genomic prediction of rhizomania resistance in sugar beet (Beta vulgaris L.) by implementing epistatic effects and feature selection

Background Rhizomania counts as the most important disease in sugar beet Beta vulgaris L. for which no plant protection is available, leaving plant breeding as the only defence strategy at the moment. Five resistance genes have been detected on the same chromosome and further studies suggested that these might be different alleles at two resistance clusters. Nevertheless, it was postulated that rhizomania resistance might be a quantitative trait with multiple unknown minor resistance genes. Here, we present a first attempt at genomic prediction of rhizomania resistance in a population that carries resistances at the two known resistance clusters. The sugar beet population was genotyped using single nucleotide polymorphism (SNP) markers. Methods First, genomic prediction was performed using all SNPs. Next, we calculated the variable importance for each SNP using machine learning and performed genomic prediction by including the SNPs incrementally in the prediction model based on their variable importance. Using this method, we selected the optimal number of SNPs that maximised the prediction accuracy. Furthermore, we performed genomic prediction with SNP pairs. We also performed feature selection with SNP pairs using the information about the variable importance of the single SNPs. Results From the four methods under investigation, the latter led to the highest prediction accuracy. These results lead to the conclusion that more than the two known resistance clusters are involved in rhizomania resistance and that genetic interactions affect rhizomania resistance. Finally, we have analysed which SNPs were repeatedly detected in the feature selection process and discovered four SNPs, two of which are located on chromosomes that were previously not associated with rhizomania resistance.

A Systems Biology Analysis of Chronic Lymphocytic Leukemia

Whole-genome sequencing has revealed that TP53, NOTCH1, ATM, SF3B1, BIRC3, ABL, NXF1, BCR, and ZAP70 are often mutated in CLL, but not consistently across all CLL patients. This paper employs a statistical thermodynamics approach in combination with the systems biology of the CLL protein–protein interaction networks to identify the most significant participant proteins in the cancerous transformation. Betti number (a topology of complexity) estimates highlight a protein hierarchy, primarily in the Wnt pathway known for aberrant CLL activation. These individually identified proteins suggest a network-targeted strategy over single-target drug development. The findings advocate for a multi-target inhibition approach, limited to several key proteins to minimize side effects, thereby providing a foundation for designing therapies. This study emphasizes a shift towards a comprehensive, multi-scale analysis to enhance personalized treatment strategies for CLL, which could be experimentally validated using siRNA or small-molecule inhibitors. The result is not just the identification of these proteins but their rank-order, offering a potent signal amplification in the context of the 20,000 proteins produced by the human body, thus providing a strategic basis for therapeutic intervention in CLL, underscoring the necessity for a more holistic, cellular, chromosomal, and genome-wide study to develop tailored treatments for CLL patients.

Clinical utility of relative telomere length analysis in pediatric bone marrow failure

IntroductionTelomere length related studies are limited in pediatric marrow failure cases due to difficulty in establishing population specific age related normograms. Moreover, there is paucity of data related to clinical relevance of telomere length in idiopathic aplastic anemia (IAA) and non telomere biology inherited bone marrow failure syndrome (IBMFS) cases. Methodology: Hence, in current study we investigated Relative telomere length (RTL) by RQ-PCR in 83 samples as: healthy controls (n = 44), IAA (n = 15) and IBMFS (n = 24). In addition, we performed chromosomal breakage studies and targeted NGS to screen for pathogenic variants. Results & Conclusion: Median RTL was significantly different between control vs. IBMFS (p-0.002), IAA vs. IBMFS (p-0.0075) and DC vs. non-DC IBMFS (p-0.011) but not between control vs. IAA (p-0.46). RTL analysis had clinical utility in differentiating BMF cases as 75 % (9/12) of DC had short/very short telomeres compared to only 17 % (2/12) of non-DC IBMFS, 7 % (1/15) of IAA and 7 % (3/44) of controls (p < 0.001).

In silico Characterization of Satellitomes and Cross-Amplification of Putative satDNAs in Two Species of the Hypostomus ancistroides Complex (Siluriformes, Loricariidae)

Introduction: The mapping of the satellite DNA on chromosomes is vital to understanding the distribution and evolution of repetitions in the genome since these chromosomal studies have shown the origin, evolutionary mode, and function of repetitive sequences. This study aimed to prospect the satellitome and determine its location in the genome of two cryptic species of Hypostomus, H. aff. ancistroides and H. ancistroides, with and without XX/XY sexual chromosome system. Methods: Mitotic chromosomes and DNA extraction were obtained according to protocols. After the whole genome sequencing, the satDNAs were retrieved, amplified, and hybridized in chromosome preparations for male and female individuals. Results: We found 30 satellite families (47 variants, two superfamilies) in H. ancistroides and 38 satellite families (45 variants, four superfamilies) in H. aff. ancistroides. The sequences varied from 14 bp to 2,662 bp in H. ancistroides and from 14 bp to 2,918 bp in H. aff. ancistroides. We did not observe any tandem repeats that were exclusive to each of the libraries; however, many sequences showed very different abundances and copy numbers between the libraries. Four satDNAs did not hybridize on the chromosomes of either species. Conversely, one satDNA hybridized in both species, HxySat1-80. However, the phenotypes found varied among species, populations, and in the same individual. There was no sign of HanSat3-464 and HanSat11-335 in any individuals of H. aff. ancistroides, but markings were in the chromosomes of H. ancistroides. HxySat12-1127 and HxySat8-52, on the other hand, were only hybridized in H. aff. ancistroides, while H. ancistroides had a negative sign. No hybridization of satDNAs was found in the X and Y sex chromosomes as they were mostly composed of euchromatin. Conclusion: We distinguish H. aff. ancistroides as genetically different from H. ancistroides, recognizing that such characteristics go far beyond morphological, karyotypic, and molecular data. Our data support the differential abundance and location of satellite DNAs and confirm that many organisms, including fish, have repetitive sequences that validate the library hypothesis. All found and validated satDNAs and the characterization of the satellitomes of the two species represent important contributions to cytogenomic studies of the genus Hypostomus.

Meiotic chromosome behaviour of a newly recorded ant-like spider, Myrmarachne melanocephala MacLeay, 1839 from Manipur, India

Cytological and chromosomal studies of ant-like spiders Myrmarachne melanocephala MacLeay, 1839, were undertaken with 12 males captured alive in the months of January to July 2023 from three habitats. The haploid count of male specimens was observed to be 13: 4 acrocentric (including X chromosome), 6 subtelocentric, 2 submetacentric, and 1 metacentric and showed X0 sex determination mechanisms, so the diploid count of the species was 25 (13+12). The single sex chromosome occupied roughly 4-6 per cent of the nuclear volume prominently in the Interphase – Prophase I stage. The structure of X chromosome in interphase stage was circular-rectangular block. The peculiar shape of rod-shaped X chromosome was maintained from early pre-leptotene stage till the end of the division particularly the Prophase I. The synapsis started early from late leptotene and duration of zygotene was long enough to visualize the perfect ones in late zygotene. There were nine diplotene bivalents with interstitial chiasma.

The role of karyosystematics in the taxonomy of the genera Sorex and Crocidura (Mammalia: Soricidae), and the state of chromosomal studies of shrews in the Russian Far East

Literature data on the chromosomal characteristics of Soricidae, genera Crocidura and Sorex are analyzed. The importance of karyological studies for shrew taxonomy at the species level in the Russian Far East is shown. For each species, information on taxonomy, distribution, collection site of studied samples and the structure of karyotypes is provided. The intraspecifi c variability of shrew karyotypes in the Russian Far East is discussed based on a comparison of chromosomal characteristics from diff erent populations located in Russia and other geographical regions.

Comparative Cytogenetics of the Malagasy Ground Geckos of the Paroedura bastardi and Paroedura picta Species Groups.

We present a comparative chromosome study of several taxa of the Malagasy ground geckos of the Paroedura bastardi and P. picta species groups. We employed a preliminary molecular analysis using a trait of the mitochondrial 16S rRNA gene (of about 570 bp) to assess the taxonomic status of the samples studied and a cytogenetic analysis with standard karyotyping (5% Giemsa solution), silver staining (Ag-NOR staining) and sequential C-banding (C-banding + Giemsa and + fluorochromes). Our results show that all the taxa studied of the P. bastardi group (P. ibityensis, P. rennerae and P. cf. guibeae) have a similar karyotype composed of 2n = 34 chromosomes, with two metacentric pairs (1 and 3) and all other pairs being acrocentric. Chromosome diversification in the P. bastardi group was mainly linked to the diversification of heteromorphic sex chromosome systems (ZZ/ZW) in P. ibityensis and P. rennerae, while no heteromorphic sex chromosome pair was found in P. cf. guibeae. The two taxa investigated of the P. picta species group (here named P. picta and P. cf. picta based on molecular data) showed the same chromosome number of 2n = 36, mostly acrocentric elements, but differed in the number of metacentric elements, probably as a result of an inversion at chromosome pair 2. We highlight that the genus Paroedura is characterized by the independent diversification of heterogametic sex chromosomes in different evolutionary lineages and, similarly to other phylogenetically related gecko genera, by a progressive formation of a biarmed element by means of tandem fusions and inversions of distinct pairs.

The First Identification of Homomorphic XY Sex Chromosomes by Integrating Cytogenetic and Transcriptomic Approaches in Plestiodon elegans (Scincidae)

The sex chromosomes of skinks are usually poorly differentiated and hardly distinguished by cytogenetic methods. Therefore, identifying sex chromosomes in species lacking easily recognizable heteromorphic sex chromosomes is necessary to fully understand sex chromosome diversity. In this paper, we employed cytogenetics, sex quantification of genes, and transcriptomic approaches to characterize the sex chromosomes in Plestiodon elegans. Cytogenetic examination of metaphases revealed a diploid number of 2n = 26, consisting of 12 macrochromosomes and 14 microchromosomes, with no significant heteromorphic chromosome pairs, speculating that the sex chromosomes may be homomorphic or poorly differentiated. The results of the sex quantification of genes showed that Calumenin (calu), COPI coat complex subunit γ 2 (copg2), and Smoothened (smo) were at half the dose in males as in females, suggesting that they are on the X chromosome. Transcriptomic data analysis from the gonads yielded the excess expression male-specific genes (n = 16), in which five PCR molecular markers were developed. Restricting the observed heterozygosity to males suggests the presence of homomorphic sex chromosomes in P. elegans, XX/XY. This is the first breakthrough in the study of the sex chromosomes of Plestiodon.

Primary amenorrhoea - cytogenetic study in 40 Indian women

Background Primary amenorrhoea (PA) refers to an ailment when adolescent girls do not attain menarche naturally. It is one of the most common gynaecological disorders specified. Chromosomal abnormalities play a pivotal role in PA. Cytogenetic analysis is an indispensable diagnostic tool to determine the abnormality of the chromosome. In an emerging country like India, cytogenetic analysis is at a nascent stage. There are very few studies on Cytogenetics present in eastern India, including West Bengal. In rural and suburban areas PA sufferers often experience late diagnosis and struggle to access suitable curative management. The aim of the study is to evaluate the various types of chromosomal abnormalities in patients suffering from PA for accurate, better management of the same and further counselling. Methods A total of 40 PA cases were referred by obstetricians and gynaecologists to the Department of Genetics of Nirnayan Health Care, Kolkata. To screen the chromosomal abnormalities, human leukocyte culture was accomplished with their peripheral venous blood followed by G-banding and then karyotyping was executed according to ISCN-2020. Result Out of 40 patients, 29 were normal among which 46,XX was found in 70% cases (n = 28) and 46,XX,9qh + in 2.5% (n = 1). The remaining 11 showed different types of abnormalities. 45,X was found in 10% (n = 4), 46,X,i(X)(q10) in 2.5% (n = 1), 46,X,del(X)(p11.2) in 2.5% (n = 1), 46,X,del(X)(p22.1) in 2.5% (n = 1), 46,X,del(X)(q24) in 2.5% (n = 1), 46,XY in 2.5% (n = 1), mos 45,X[22]/46,Xi(X)(q.10)[8] in 2.5% (n = 1) and mos 45,X[16]/46,XY[14] (2.5%) in 2.5% (n = 1). Conclusion This study indicates the importance of chromosomal study which must be included in early diagnosis of PA. Karyotyping at the appropriate phase of life will not only help in the judicial management of this disorder but will also give young girls a better lifestyle.

Chromosomal abnormalities study for anembryonic pregnancy by BACs-on-Beads technique

ObjectiveThis study evaluated the BACs-on-Beads™ (BoBs) efficiency assay in detecting chromosomal anomalies in products of conception (POC) specimens associated with anembryonic pregnancy (AP) among Thai pregnant women. MethodRetrospective analysis applied the BoBs™ assay to examine AP samples from 2010 to 2022. The incidences of AP with chromosomal abnormalities were reported. ResultAssessment of villi from anembryonic pregnancy samples found normal chromosome complement in 50% of the cases, while the remainder showed chromosomal abnormalities. Trisomy 16 was found in 15% of the cases and trisomies 22, 15, and 19 in 9.6%, 3.8%, and 3.8%, respectively. Advanced maternal age was associated with a higher incidence of aneuploidy. ConclusionThe BoBs™ assay effectively detected diverse chromosomal abnormalities in villi samples from POC. The diagnostic utility of the BoBs™ assay was highlighted in identifying chromosomal irregularities in AP cases. Trisomy 16 possessed the most chromosomal abnormalities in the AP samples.

Dried storage of sperm at supra-zero temperatures: An alternative for flow cytometric analysis under field conditions

In biotechnological processes such as chromosomal manipulation studies, semen has become a reference in the ploidy verification of the evaluated material. However, the use of fresh samples is limited to the use at field conditions because the analysis is performed under laboratory conditions. Thus, this study aimed to develop a simpler procedure for storing dry semen at 28 °C to reduce cold storage costs. For this, semen samples were evaluated according to established quality semen parameters, a protocol for dry, and 3 sterilization treatments of dry semen were applied to the store. The integrity of the DNA was evaluated every two months, using fresh semen, dry semen (untreated), and particles 3C to compare the peaks by flow cytometry. The results indicated that all samples evaluated before and after drying showed no significant difference in the DNA content. UV-treated semen showed a 1C peak in the histogram up to 180 days of storage and a non-significant difference (P > 0.05) from fresh control in the number of DNA particles up to 120 days and untreated only showed a 1C peak up to 120 days. The developed method may become an interesting procedure to serve as a reference peak for practical flow cytometric analysis, not only in the field of fish biology but also in biomedical and agricultural sciences. Furthermore, dried semen can become a tool for the preservation of genetic material and is a promising low-cost storage technique for biobanking.

Clinical, pathologic, and genomic characteristics of two pediatric glioneuronal tumors with a CLIP2::MET fusion

Integration of molecular data with histologic, radiologic, and clinical features is imperative for accurate diagnosis of pediatric central nervous system (CNS) tumors. Whole transcriptome RNA sequencing (RNAseq), a genome-wide and non-targeted approach, allows for the detection of novel or rare oncogenic fusion events that contribute to the tumorigenesis of a substantial portion of pediatric low- and high-grade glial and glioneuronal tumors. We present two cases of pediatric glioneuronal tumors occurring in the occipital region with a CLIP2::MET fusion detected by RNAseq. Chromosomal microarray studies revealed copy number alterations involving chromosomes 1, 7, and 22 in both tumors, with Case 2 having an interstitial deletion breakpoint in the CLIP2 gene. By methylation profiling, neither tumor had a match result, but both clustered with the low-grade glial/glioneuronal tumors in the UMAP. Histologically, in both instances, our cases displayed characteristics of a low-grade tumor, notably the absence of mitotic activity, low Ki-67 labeling index and the lack of necrosis and microvascular proliferation. Glial and neuronal markers were positive for both tumors. Clinically, both patients achieved clinical stability post-tumor resection and remain under regular surveillance imaging without adjuvant therapy at the last follow-up, 6 months and 3 years, respectively. This is the first case report demonstrating the presence of a CLIP2::MET fusion in two pediatric low-grade glioneuronal tumors (GNT). Conservative clinical management may be considered for patients with GNT and CLIP2:MET fusion in the context of histologically low-grade features.

What is a B chromosome? Early definitions revisited.

Since the discovery of B chromosomes, multiple different definitions of these selfish genetic elements have been put forth. We reconsidered early definitions in light of recently published studies. While there are many characteristics that vary among different B chromosomes, such as their evolutionary origins, size, segregation behaviors, gene content, and function, there is one defining trait of all B chromosomes: they are nonessential for the organism. The points raised here may be useful for framing future B chromosome studies and help guide the categorization of new chromosomal elements that are uncovered in genomic studies.

First cytogenetic study of the Somphong’s rasbora (Trigonostigma somphongsi) (Perciformes, Cyprinidae), a critically endangered species in Thailand

The first chromosome study of Trigonostigma somphongsi (Meinken,1958) from Thailand. Specimens were collected from Pak Phli District, Nakhornnayok Province, central Thailand. The mitotic chromosomes were directly prepared from kidney tissues of two males and two females. Conventional staining and Ag-NOR banding techniques were applied to stain the chromosomes. The results shown that diploid chromosome number of T. somphongsi was 2n=50, the fundamental numbers (NF) were 92 in both male and female. The types chromosomes consisted of 10 metacentric, 20 submetacentric, 12 acrocentric and 8 telocentric chromosomes. The result also exhibited that the interstitial nucleolar organizer regions (NORs) were clearly observed at the short arm of chromosome pair 2. The karyotype formula could be deduced as: 2n (diploid) 50=10m+20sm+12a+8t.

Bone marrow histology of cytopenias : Contribution to hematological differential diagnosis

Besides microscopic evaluation of smears, flow cytometric analysis, chromosomal and molecular studies, histological analysis of bone marrow biopsies (BMbx) is animportant component of multiparameter diagnostics of cytopenias in hematology. More than in other fields of histopathology, correct interpretation of BMbx requires correlation with the results of these further studies and other clinical findings. Microcytic, normocytic and macrocytic anemia, isolated granulocytopenia and thromobocytopenia as well as pancytopenia represent frequent and recurrent diseases. With regard to aetiology, reactive and neoplastic causes must be differentiated. Reactive causes of cytopenia include substrate deficiencies, enhanced turn over and loss, and inflammatory processes. Neoplastic disorders with the exception of myeloproliferative neoplasms generally manifest as cytopenia and comprise myelodysplastic syndromes (MDS), acute myeloid leukemia (AML) and lymphoma.

Balanced spatiotemporal arrangements of histone H3 and H4 posttranslational modifications are necessary for meiotic prophase I chromosome organization.

Dynamic nuclear architecture and chromatin organizations are the key features of the mid-prophase I in mammalian meiosis. The chromatin undergoes major changes, including meiosis-specific spatiotemporal arrangements and remodeling, the establishment of chromatin loop-axis structure, pairing, and crossing over between homologous chromosomes, any deficiencies in these events may induce genome instability, subsequently leading to failure to produce gametes and infertility. Despite the significance of chromatin structure, little is known about the location of chromatin marks and the necessity of their balance during meiosis prophase I. Here, we show a thorough cytological study of the surface-spread meiotic chromosomes of mouse spermatocytes for H3K9,14,18,23,27,36, H4K12,16 acetylation, and H3K4,9,27,36 methylation. Active acetylation and methylation marks on H3 and H4, such as H3K9ac, H3K14ac, H3K18ac, H3K36ac, H3K56ac, H4K12ac, H4K16ac, and H3K36me3 exhibited pan-nuclear localization away from heterochromatin. In comparison, repressive marks like H3K9me3 and H3K27me3 are localized to heterochromatin. Further, taking advantage of the delivery of small-molecule chemical inhibitors methotrexate(heterochromatin enhancer), heterochromatin inhibitor, anacardic acid (histone acetyltransferase inhibitor), trichostatin A (histone deacetylase inhibitor), IOX1 (JmjC demethylases inhibitor), and AZ505 (methyltransferase inhibitor) in seminiferous tubules through the rete testis route, revealed that alteration in histone modifications enhanced the centromere mislocalization, chromosome breakage, altered meiotic recombination and reduced sperm count. Specifically, IOX1 and AZ505 treatment shows severe meiotic phenotypes, including altering chromosome axis length and chromatin loop size via transcriptional regulation of meiosis-specific genes. Our findings highlight the importance of balanced chromatin modifications in meiotic prophase I chromosome organization and instability.

Comparative cytogenetics of the families Pteromalidae and Spalangiidae – a review

AbstractAlthough chromosomes of only 20 members of Pteromalidae sensu lato (s.l.), which belong to the families Pteromalidae sensu stricto (hence Pteromalidae) and Spalangiidae, are studied up to now, the accumulated cytogenetic information has important implications for taxonomic and evolutionary studies of these parasitoids. Within the former family, which includes the overwhelming majority of karyotypically studied species of Pteromalidae s.l., the known haploid chromosome number (n) can vary from 4 to 7 in Pachycrepoideus vindemmiae (Rondani) and Anisopteromalus calandrae (Howard), respectively, with a clear mode at n = 5. Among these parasitoids, Nasonia vitripennis (Walker) is the most thoroughly studied species in terms of modern cytogenetic techniques. On the contrary, chromosomes of only two members of Spalangiidae are known, both belonging to the Spalangia endius Walker complex, with n = 4 and 6. A few cosmopolitan cryptic species of the family Pteromalidae were studied using cytogenetic approaches. Specifically, Anisopteromalus quinarius Gokhman et Baur, a newly described parasitoid of stored‐product pests with n = 5, was initially separated from A. calandrae based on its different chromosome number. Another pteromalid with a similar biology, Lariophagus distinguendus (Förster), was also found to harbor two cryptic species with n = 5 and 6. Moreover, a morphometric study of these karyotypes suggested that the largest chromosome in the set with n = 5 has resulted from a fusion of two particular chromosomes in the karyotype with n = 6, and this hypothesis was confirmed using microdissection and whole‐chromosome painting. Recent cytogenetic and bioinformatic research also showed that N. vitripennis, Nasonia longicornis Darling, Nasonia giraulti Darling, Nasonia oneida Raychouhury et Desjardins, Muscidifurax uniraptor Kogan et Legner, and Trichomalopsis sarcophagae (Gahan) (all Pteromalidae) share the TTATTGGG telomeric motif with most other Chalcidoidea. Perspectives of the chromosome study of Pteromalidae s.l. are briefly discussed.

Abstract A030: Fusion between macrophages and cancer cells up-regulates signal regulatory protein pathway and contributes to malignant progression of pancreatic cancer after radiation

Abstract Introduction: Fusion between tumor cells with leukocytes contributes to tumor heterogeneity, resulting in tumorigenesis, metastasis, and treatment resistance. Recent studies demonstrate that an inflammatory microenvironment enhances tumor-macrophage fusion. We hypothesize that tumor-macrophage fusion hybrids contribute to radiation induced pancreatic cancer progression. Materials and Methods: Tumor tissues of female patients receiving previous bone marrow transplantation (BMT) from male donors due to leukemia/lymphoma were collected for Y chromosome and immunofluorescence study. Murine subcutaneous tumor models of cre-loxP or dual fluorescence system were established to demonstrate fusion between Pan02, a murine pancreatic adenocarcinoma cell line, and stromal cells of ROSA (Gt(ROSA)26Sor tm4(ACTB-tdTomato,-EGFP)Luo/Jnarl) mice with or without local radiation exposure. KC (pdx-1-cre-KrasLSL-G12D) mice, were given whole body irradiation followed by BMT from ROSA mice to measure fusion between pancreatic cancer and hematopoietic cells. Liposomal chlodronate, a macrophage depleting agent, and immunofluorescence staining of fusion hybrids in ROSA mice tumors were used to demonstrate macrophage as a fusion partner. Fusion hybrid clones of murine/human pancreatic adenocarcinoma cells with macrophages were selected from co-culture and sorting followed by studies including ploidy, clonogenicity, migration and radio-sensitivity. Affymetrix microarray analysis was used to find differentially expressed genes of fusion hybrids. Results: Fusion phenomenon was demonstrated by showing colocalization of Y chromosomes with epithelial markers in cancer tissues from female patients receiving prior BMT from male donors. Fusion hybrids were found in pancreas tumors of KC mice after BMT from ROSA mice. Fusion hybrids within tumors increased by time, three folds within 6 weeks; and 2.5 folds after 20Gy radiation exposure. Liposomal clodronate reduced fusion hybrids and tumor growth. Immunofluorescence stain of tumor tissues demonstrated CD11b(+) macrophage to be the major fusion partner. Purified Fusion hybrids showed enhanced migration, proliferation, aneuploidy and radio-resistance. Model based gene analysis of microarray study disclosed signal regulatory protein (SIRP) signal pathway was significantly upregulated in fusion hybrids. Upregulated SIRP signal molecules, including DAP12, PyK2, were validated by immunoblots. Silencing DAP12 in myeloid cells from human peripheral blood showed decreased fusion rate with Panc-1 cells. DAP12mRNA depletion in Panc-1 fusion hybrids disclosed enhanced radio-sensitivity. Defactinib (VS6063), a PyK2 inhibitor, reduced fusion phenomenon and suppressed pancreatic tumor growth of mice after local radiation. Conclusions: Fusion between pancreatic cancer cells and macrophages contribute to radiation enhanced malignant progression of pancreatic cancer. SIRP signal pathway is a potential target to disrupt fusion phenomenon and ameliorate pancreatic cancer progression after radiation. Citation Format: Hui Ju Ch'ang, Yi-Chih Tsai, Ting Wei Li, Rui-Jun Liu, Tze-Sing Huang, Sse-Pei Wan, Su-Liang Chen, Shih-Sheng Jiang. Fusion between macrophages and cancer cells up-regulates signal regulatory protein pathway and contributes to malignant progression of pancreatic cancer after radiation [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A030.