A new study demonstrated the power of WGS to comprehensively and accurately profile the genetic abnormalities in cases of childhood B-ALL that were previously studied with standard cytogenetics, FISH and MLPA (Ryan et al., 2023). Two cohorts with a total of 210 patients were studied. One cohort carried cytogenetic abnormalities of known significance (n=38). The other cohort (n=172) lacked cytogenetic abnormalities detectable by standard methods (B-other ALL group), and was treated within the UKALL2003 clinical trial. The WGS approaches used were a tumor-normal (T-N) pipeline and a tumor-only (T-only) pipeline. Most patients (202/210) carried a distinct abnormality already known or a new one that defined a genetic subtype. WGS identified almost all the abnormalities in the cohort with typical cytogenetic abnormalities previously detected (37/38 in the T-only pipeline, 34/38 in the T-N pipeline). The B-other ALL cohort showed two types of abnormalities by WGS. Some were cytogenetic abnormalities emblematic of B-ALL that were missed by previous standard methods (19/172 cases) due to poor samples or incomplete testing at the time of diagnosis. The remaining abnormalities were cryptic (145/153 cases) and defined genetic subtypes. Some new molecular variants emerged with WGS, the profile of PAX5 rearrangements and the ETV6::RUNX1-like subtype was characterized in more detail, and the detection of DUX4 rearrangements was markedly improved by a novel bioinformatic pipeline. Whole transcriptome sequencing (WTS) conducted in a subset of 85 patients was consistent with the results of WGS and standard cytogenomic techniques. This study validated the diagnostic use of WGS to uncover and characterize in detail the genetic aberrations in pediatric B-ALL. As a result, Ryan et al. endorsed the routine use of WGS to discover more abnormalities of clinical significance that define new genetic subtypes, as well as to improve diagnosis, risk stratification, and therapy.
The latest study with whole genome sequencing (WGS) in pediatric B-ALL validated its use as a standalone test to detect underlying clinically significant genetic abnormalities (Rezayee et al., 2023). This was a retrospective molecular survey in bone marrows previously collected and stored from 88 patients who were enrolled in NOPHO trials. The testing was done through 150 bp paired-end WGS applied to a paired analysis of leukemia-germline samples (L-N) (n=64), and to the analysis of leukemia-only samples (L) (n=88). The results demonstrated a full concordance between both WGS approaches and between the results from WGS and previous standard of care tests (SOCTs). All the mandatory aberrations that require testing in the current ALLTogether trial protocol were identified in 38 patients. In addition, WGS accurately identified the majority of aberrations characteristic of B-other ALL (35/36 cases), copy number abnormalities (CNAs) in eight critical genes or regions, CNAs that characterize the IKZF1plus profile, and the abnormalities in patients with Down syndrome. An adapted methodology was necessary for the detection of DUX4::IGH rearrangements in four patients. A comparison between sequencing coverages of 90X and 30X demonstrated that a lower 30X coverage was sufficient to detect all the relevant abnormalities. This successful testing was accomplished through filtering of WGS data focusing on just genes and genomic regions that are routinely implicated in pediatric B-ALL. As a result, it simplified the extraction of data and facilitated the interpretation of results. Overall, the precise identification of abnormalities that was accomplished by WGS allowed the assignment of patients to distinct genetic subtypes. The conclusion of this study was that WGS is quite reliable and can replace the use of SOCTs to profile pediatric B-ALL.
Myxoid/Round Cell Liposarcoma (MRCL) is characterized as a soft tissue sarcoma that is associated with unusual patterns of metastasis to extrapulmonary sites, such as bones and other soft tissue sites. Here, we present a case of a 48-year-old male patient, diagnosed with MRCL. The patient presented with a grade 1 myxoid liposarcoma in his left leg. DNA FISH analysis showed variant rearrangements of the EWSR1 (22q12) gene and loss of the 5' DDIT3 (CHOP 12q13) gene. The variant rearrangement showed one or two fusions with multiple separated (rearranged) signals. The EWSR1-DDIT3 rearrangement has been reported in MRCL. The variant rearrangements of the EWSR1 (22q12) gene findings correlate with concurrent conventional cytogenetic findings and were described as nuc ish(EWSR1x2) (5'EWSR1 sep 3'EWSR1x1)[128/100],(5'EWSR1,3'EWSR1)x1~3(5'EWSR1 con 3'EWSR1x1~2)[57/100]. The variant rearrangements of the DDIT3 (CHOP 12q13) gene findings were described as nuc ish(5'DDIT3x1,3'DDIT3x2)(5'DDIT3 con 3'DDIT3x1)[195/200]. Molecular cytogenetic studies also showed a rearrangement of EWSR1 (22q12) in 64% of nuclei and variant rearrangement in 31.5% of nuclei. A loss of DDIT3's (12q13) 5' signal was found in 97.5% of interphase nuclei. Molecular pathology results indicated the patient was positive for EWSR1 (exon 7) and DDIT3 (exon 2) fusion. The patient underwent radiation therapy pre-resection of the myxoid liposarcoma. The most common form of MRCL is associated with t(12;16)(q13;p11), leading to FUS-CHOP and EWS-CHOP fusion proteins acting as aberrant transcription factors. The key element here is that this EWSR1-DDIT3 rearrangement led to a translocation t(12;22)(q13;q12) which is a rare cytogenetic event that led to the development of MRCL in this patient.
The Nobel Assembly of the Karolinska Institute (Sweden) awarded the 2024 Nobel Prize in Physiology or Medicine to Dr. Victor Ambros (University of Massachusetts Chan Medical School, Worcester, United States) and Dr. Gary Ruvkun (Massachusetts General Hospital, Boston, United States). This award recognized their joint discoveries of microRNAs and a novel mechanism of post-transcriptional regulation of gene expression in the worm C. elegans. This revolutionary breakthrough demonstrated first that miRNAs provide a refined control of development in C. elegans targeting mRNAs from distinct genes in an orderly fashion. Subsequent discoveries of many more microRNAs in other organisms across a wide evolutionary tree showed that these molecules and the regulatory mechanism of gene expression that they regulate are conserved throughout evolution. With more studies, these advances also triggered a realization that microRNAs play important roles in various critical biological processes (e.g., cellular growth, differentiation, development, cellular physiology, etc.). Other surveys reported abnormalities in microRNAs connected to multiple human diseases which, in turn, generated research interest in potential treatments focused on faulty microRNAs and their evaluation as potential markers of disease. This Nobel Prize caps nearly three decades of unprecedented advances in RNA research that include similar awards. A 2006 Nobel Prize honored the discovery of RNA interference that was initially described in 1998. The 2023 Nobel Prize paid tribute to the first effective human mRNA vaccines. Both advances generated practical applications of high significance including medical uses in humans. For these reasons, there is hope that in due time it will also be the case with microRNAs given their biological potential and many relevant physiological functions that they control.
Two recent studies that re-examined through novel approaches previous shotgun sequencing data from prehistoric/historic Europeans uncovered several autosomal and sex chromosome aneuploidies (Anastasiadou et al., 2024; Rohrlach et al., 2024). These disorders, which are common in contemporary humans, were trisomies 18 and 21, Klinefelter syndrome (47,XXY), 47,XYY syndrome, and mosaic Turner syndrome X/XX. These discoveries about prehistoric/historic occurrence of constitutional chromosomal syndromes with high clinical significance in modern medical genetics are an important breakthrough. They contribute to a more comprehensive genetic delineation of past human populations and give impetus to perform more historic/prehistoric studies to discover other contemporary genetic disorders. A molecular profiling of ancient DNA (aDNA) from human remains added to anthropological and archaeological data may also give a broader picture of the social and historical contexts of individuals who were affected by genetic diseases. These advances in the detection of chromosome aneuploidies and previous discoveries of current monogenic syndromes in archaic hominins also highlight the possibility of detecting other genetic diseases of present-day occurrence in our ancestors. As a result, it might be feasible to delineate the evolutionary history of modern genetic diseases, establishing a timeline of their emergence, patterns of mutations, putative mechanisms of selection, and genomic mechanisms involved.
B-cell acute lymphoblastic leukemia (B-ALL) can afflict both adult and pediatric patients and is characterized by a build-up of B lymphoblasts. Here we present a case of a 25-year-old male patient with a history of B-ALL. Ninety percent of the bone marrow revealed pancytopenia with sheets of B lymphoblasts consistent with the diagnosis of B-ALL for acute pre-B lymphoblastic leukemia. The immunophenotype also presented predominant immature precursor B lymphoid cells positive for CD19, CD10, CD34, CD58, CD38, CD9, and TdT. Chromosome analysis of the bone marrow showed a complex karyotype described as 45~47,XY,i(8)(q10),der(10)add(10)(p11.1)add(10)(q23),-20,+1~2mar[cp3]/46,XY[36]. While IGH rearrangements were cryptic cytogenetically, DNA FISH analysis showed evidence of the IGH (14q32.2) gene rearrangement in 96.5% of the nuclei examined. These results were described as nuc ish(IGHx2)(5'IGH sep 3'IGHx1)[187/200],(5'IGH,3'IGH)x1~4(5'IGH con 3'IGHx0~2) [6/200]. The remaining probes were normal. Further studies using the MYC/IGH DC, DF probe from Abbott showed a gain of IGH signal in 7.5% of the nuclei examined: nuc ish(MYCx2,IGHx3)[15/200]. Metaphase FISH also showed that what appeared to be an isochromosome 8q was a derivative chromosome 8 defined as add(8)(p11.2) that contained a green IGH signal. In light of these results the karyotype was characterized as 45~47,XY,add(8)(p11.2),der(10)add(10)(p11.1)add(10)(q23),-20,+1~2mar[cp3].ish add(8) (p11.2) IgH+. IgH abnormalities are rare in B-ALL and are usually associated with a poor prognosis. However, at the present time our patient presented no evidence of persistent or residual disease and a cytogenetic response to the present therapy.
B-cell acute lymphoblastic leukemia (B-ALL) is one of the prevalent pediatric leukemias, accounting for 26% of cancers diagnosed in children 0-14 years of age. We present a case report of an 11-year-old girl with B-ALL. The patient was in complete remission nine months after diagnosis but passed away a month later from chemotherapy-induced hepatic failure, renal failure, and febrile neutropenia. Conventional cytogenetics showed a karyotype of 46,XX,del(5)(q31q35),add(6)(q23),del(7)(q32q36),add(11)(q23),ider(21)(q10)add(21) (q22),inc[20]. DNA FISH analysis performed on the bone marrow showed variant rearrangement of CRLF2, as well as loss of ETV6 signals and gain of RUNX1 signals. The presence of CRLF2 rearrangements within the context of a complex karyotype is often associated with CRLF2 overexpression and poor prognosis. The heterogeneity of B-ALL and the variability in the outcomes of patients that lack characteristic genetic abnormalities highlight the importance of profiling unusual genetic cases such as this one and continuing research to understand the molecular mechanisms of rarer mutations.
A recent prospective study run by the IDENTIFY project at the U.S. National Institutes of Health (NIH) uncovered occult cancers in pregnant or postpartum women who previously received Non-Invasive Prenatal Testing (NIPT) reports of atypical abnormal/ unreportable results that were discordant with the fetal genotype. Among 107/117 patients enrolled who received a full evaluation, 52 (48.6%) had cancers, mostly lymphomas (31/52), colorectal tumors (9/52), and breast cancer (4/52). These results were gathered through standardized research cfDNA sequencing in peripheral blood and a comprehensive cancer screening protocol. Most of these patients (47/52) showed a sequencing pattern in cfDNA of multiple subchromosomal and/or whole gains and losses in multiple chromosomes (≥3). This pattern was interpreted as a high-risk indicator of cancers. Except for whole-body MRI imaging, which was very effective in discovering tumors (49/101 cases), the rest of the cancer screening was not informative. The whole data strengthen the view that NIPT has clinical value for a preliminary identification of pregnant women who may have hidden malignancies and should be referred for a thorough cancer screening. In addition, a uniform follow-up protocol of comprehensive cancer screening allowed the diagnosis of a substantial number of cancers that otherwise would not have been detected. Overall, these results from IDENTIFY, the first via a prospective study, also represent progress in guidelines for improved identification and management of occult malignancies coexisting with pregnancies.
Chronic myeloid leukemia (CML) is typically characterized by the presence of the BCR-ABL1 fusion gene on chomosome 22 resulting from a t(9;22)(q34;q11.2) translocation. We report a case of a 59-year-old female with CML in the chronic phase, initially presenting with thrombocytosis and diagnosed with t(9;22) via conventional karyotyping and fluorescence in situ hybridization (FISH). Nine years and seven months after the initial diagnosis, despite treatment with standard imatinib mesylate therapy (400 mg daily), conventional cytogenetic analysis revealed the emergence of trisomy 8 and a pericentric inversion of chromosome 16 (inv(16) (p13q22)) in cells that already carried the t(9;22). Bone marrow aspiration and biopsy showed 80% blasts, predominantly expressing myeloid markers CD13, CD33, CD117, along with HLA-DR and CD34. Both FISH and conventional karyotyping confirmed the presence of trisomy 8, inversion of chromosome 16, and t(9;22). Additionally, reverse transcription-polymerase chain reaction (RT-PCR) confirmed the presence of the BCR-ABL fusion gene. The coexistence of these genetic abnormalities is often associated with an aggressive clinical course, rapid disease progression, and chemotherapy resistance. Following disease progression, the patient was treated with a combination of hydroxyurea (500 mg) and decitabine (50 mg), and her tyrosine kinase inhibitor (TKI) therapy was switched to bosutinib (400 mg). Despite these interventions, she developed pleural effusions and lung metastases and ultimately passed away approximately seven months after initiating the new treatment due to relapsed disease and infectious complications.
Acute myeloid leukemia (AML) is a blood cancer characterized by the overproduction of myeloid precursors within the bone marrow, resulting in disrupted hematopoiesis. Chromosomal abnormalities provide valuable insights into the development of AML and serve as key indicators of patient outcomes and treatment strategies. Numerous genetic abnormalities can be seen in AML. Here, we describe a case of a 34-year-old patient with AML-M5. Biopsy and immunophenotyping confirmed AML-M5, while conventional cytogenetic and fluorescence in situ hybridization (FISH) analysis revealed trisomy of chromosomes 7 and 12, and an isochromosome (i)(Xq10). Trisomies of such chromosomes and i(Xq10) in combination are rare and carry different prognostic significance. In this case, the patient died within three days of diagnosis, demonstrating a poor prognosis. Hence, identification of such numerical chromosomal abnormalities in AML-M5 can help in patient stratification, tailored medicine, and risk assessment.
Identifying therapy-related AML (t-AML) of newly diagnosed acute leukemias is of great interest. Development of t-AML can occur after cytotoxic chemotherapy and/or radiation. We report a case of t-AML with CBFB::MYH11 fusion in a patient with a distant history of treated stage IIIB nodular sclerosing Hodgkin's lymphoma. We present the clinical course of the patient and the methods used to detect and monitor the rearrangement. Core binding factor AML (CBF-AML) after exposure to treatment is considered to be a good prognostic marker. The identification of these favorable AML subtypes such as CBF-AML highlights the importance of identifying genetic alterations, especially with increasing incidences of t-AML due to changes in choice of treatment and prognosis.
Acute myeloid leukemia, myelodysplasia-related (AML-MR) is a particularly aggressive and adverse subtype of acute myeloid leukemia, predominantly affecting older adults who often face complex treatment challenges and poor prognoses. The majority of AML-MR patients fail to achieve remission, leading to significantly reduced overall survival rates. In light of these dire outcomes, staying informed about the most recent advancements in AML-MR research and clinical practice is imperative. This review examines the latest World Health Organization classifications of AML-MR, highlighting this disease's prevalent mutations and cytogenetic abnormalities. Furthermore, we explore recent therapeutic developments, including the introduction of targeted therapies and hypomethylating agents, which offer promising avenues for improving patient outcomes. The reclassification of AML-MR underscores the critical role of genetic profiling in elucidating its pathology and guiding therapeutic strategies. Future research should focus on developing personalized treatment approaches that address the intricate genetic and clinical complexities of AML-MR, aiming to enhance survival rates and improve the quality of life for affected patients.
Penile cancer, while relatively rare compared to other male malignancies, has seen an increased global incidence, with 36,068 new cases reported in 2020. This condition primarily affects regions with low human development indexes, notably India, China and Brazil. The mainstay of treatment is often partial or total penectomy, which has a profound impact on patients' emotional and social lives. Due to limited options for early diagnosis, non-surgical treatments, restricted healthcare funding and the negative consequences of mutilating surgeries, penile cancer is often considered a neglected disease. Penile cancer exhibits various histological types, but penile squamous cell carcinoma (SCC) is the most prevalent, accounting for 95% of cases worldwide. Multiple risk factors are associated with this condition, largely tied to lifestyle behaviors, such as promiscuous sexual behavior, zoophilia, poor hygiene, phototherapy, smoking and obesity. Human papillomavirus (HPV) infection is a significant etiological factor, particularly in squamous cell carcinomas. The prevalence of HPV in penile neoplasia varies widely, and its association with mortality remains uncertain.
We present a case study of a 73-year-old female with a history of pancytopenia. The bone marrow core biopsy was suggestive of a myelodysplastic syndrome, unspecified (MDS-U). Chromosomal analysis of the bone marrow revealed an abnormal karyotype including gain of chromosomes 1, 4, 6, 8, 9, 19, and 20 in addition to loss of chromosomes 11, 13, 15, 16, 17, and 22. Also, additional material of unknown origin was found on 3q, 5p, 9p, 11p, 13p, 14p, and 15p; there were two copies of 19p, a deletion of 8q, and numerous unidentified rings and markers were present. This was characterized as: 75~77,XXX,+1,der(1;6)(p10;p10),add(3)(q27),+4,add(5)(p15.1),+6,+8,del(8)(q24.1),+add(9)(p24),-11,add (11) (p13),-13,add(13)(p10),add(14)(p11.2),-15,add(15)(p11.2), -16,-17,+19,add(19)(p13.3)x2,+20,-22, +0~4r,+4~10mar[cp11]/46,XX[8]. The cytogenetic analysis correlates with the concurrent FISH study which was positive for additional signals of EVI1(3q26.2), TAS2R1 (5p15.31), EGR1 (5q31.2), RELN (7q22), TES (7q31) RUNX1T1 (8q21.3), ABL1 (9q34), KMT2A (11q23), PML (15q24.1), CBFB (16q22), RARA (17q21), PTPRT (20q12), MYBL2 (20q13.12), RUNX1 (21q22.12) and BCR (22q11.2). Hyperdiploid karyotypes within the context of complex structural abnormalities are rare events usually associated with a poor prognosis in MDS.
Acute promyelocytic leukemia (APL) is cytogenetically characterized by the t(15;17)(q22;q21) translocation generating the PML::RARA fusion gene. Accurate laboratory diagnosis is essential for disease confirmation and prognostic prediction. In our cytogenetics laboratory, conventional GTG-banded karyotyping and fluorescence in situ hybridization (FISH) are routinely performed for all APL-suspected cases received from the chemotherapy unit of The Gujarat Cancer and Research Institute, Ahmedabad, after bone marrow/IPT requisitions. To document the cytogenetic abnormalities detected in APL-suspected cases using karyotyping and FISH, and to analyze their association with overall patient survival outcomes. This retrospective study included 32 APL-suspected cases referred to our laboratory. Each case underwent conventional cytogenetic analysis and FISH for the PML::RARA fusion. Clinical outcomes (Normal/Recovered, Discharged/Stable, Expired) were obtained from hospital records solely for correlation. Statistical analysis using SPSS included cross-tabulation and chi-square testing to assess the association between FISH status and patient outcomes. FISH detected PML::RARA fusion in 78.1% of cases (25/32), while 21.9% (7/32) exhibited negative or variant fusion patterns. All successful karyotyping studies demonstrated t(15;17), with occasional additional abnormalities. FISH-positive patients showed significantly better recovery rates (60%) compared to none among FISH-negative/variant cases. The association between FISH status and outcome was statistically significant (χ² = 11.165, p = 0.004). Cytogenetic evaluation using karyotyping and FISH provides essential diagnostic and prognostic insight in APL-suspected cases. FISH positivity strongly correlates with favorable outcomes, underscoring its value in routine diagnostic workflows.
We report a 76-year-old male patient with myelodysplastic syndrome (MDS) with a t(9;22) and deletion 20q only by FISH. Past medical history is significant for prostate cancer status post radiation therapy and a 28-pack-year smoking history. In 2016, the patient developed a DVT and incidentally was found to have a BCR::ABL1 (p210) by PCR analysis (level of 0.54% of the international scale). Subsequent bone marrow aspiration revealed a hypercellular bone marrow with a small monoclonal B-cell population morphologically consistent with chronic myelogenous leukemia (CML). FISH analysis demonstrated t(9;22) translocation and a loss of 20q12 in 5% of nuclei. The patient was started on nilotinib therapy. Follow-up BCR::ABL1 testing six months later did not detect BCR::ABL1; however, subsequent FISH analysis on bone marrow aspirates performed at one and seven years after initial diagnosis continued to show deletion 20q (1-3% of nuclei). Morphologic features of bone marrow aspirates have demonstrated a CML-type hypercellular bone marrow with myeloid/megakaryocytic hyperplasia and micromegakaryocytes. This case pinpoints the importance of comprehensive study when MDS is present with deletion 20q and a t(9;22), as it can be misdiagnosed as CML. While definitive therapeutic guidelines have yet to be established for this rare presentation of MDS, the use of tyrosine kinase inhibitors is under investigation.
Background: Prostate Cancer (PCa) is a leading cause of cancer deaths in older men worldwide. In the phosphatidylinositol 3-kinase (PIK3)/AKT pathway, the PTEN (10q23.3) gene is a negative regulator and a tumor suppressor gene frequently deleted in PCa. Information about the PTEN deletion in the primary tumor, in addition to clinico-pathological parameters, might be of significance for selecting the ideal treatment for a patient. Therefore, the aim of the present study was to determine the frequency of PTEN deletion in prostate cancer using FISH technique. Materials and Method: Histopathologically proven and diagnosed PCa patients were included for a PTEN gene deletion study by FISH technique. FISH was performed on paraffin embedded tissue using ZytoLight SPEC PTEN/CEN10 Dual Color Probe Kit (CytoVision GmbH, Bremerhaven, Germany). Results: A total of 42 histopathologically proven and diagnosed PCa patients were enrolled in the present study. The median age was 65 years. PTEN gene deletion was positive in 24 patients (57%) while 18 (43%) were negative. PTEN gene deletion was significantly higher in advanced stages as compared to those in early advanced stages. PTEN gene was significantly deleted in patients with the presence of positive lymph nodes compared to patients without positive lymph nodes. Conclusion: The present study suggests that PTEN deletion is associated with tumor stage and lymph node status. This study demonstrated that a higher rate of PTEN deletion is associated with advanced stage cancers with a Gleason's score of 7, which explains the poor prognosis associated with its deletion. Detection of PTEN status will help to identify the specific subsets of patients who might benefit from molecular targeted therapies.
The ribosomal protein S14 (RPS14) gene located at 5q33 codes for a protein involved in ribosomal biogenesis. The RPS14 gene has a length of 5.9 kb of DNA comprising 5 exons and 4 introns. It is possible that RPS14 is involved in the formation of pre-RNA 18s, an intermediate RNA that serves for the formation of the 40S small subunit of the ribosome. RPS14 haploinsufficiency (HI) produces alterations in intermediate RNA levels (pre-RNA 30S/18SE/18S), which are found in del(5q) MDS. In addition, RPS14 haploinsufficiency results in the formation of the MDM2 (double minute mouse E3 ubiquitin ligase)-RP (ribosomal protein) complex that prevents the MDM2-p53 interaction, generating an accumulation of p53 levels. This accumulation produces cell cycle arrest, impaired DNA repair, senescence, and apoptosis. RPS14 haploinsufficiency has been seen in MDS. Altered expression levels of RPS14 have also been reported in glioma, colorectal cancer, hepatocellular carcinoma, breast cancer, renal cell carcinoma, and primary myelofibrosis.
We describe a case of a 13-year-old male who presented with fatigue, loss of appetite, and weakness. Flow cytometric analysis of the bone marrow aspirate demonstrated an abnormal population of myeloid blasts, comprising approximately 48% of total events, suggesting acute myeloid leukemia (AML). The cells express CD45(dim+), CD34(+), CD117(+), CD33(+), CD13(dim+), HLADR(+), CD38(+), CD123(weak+), CD11b(weak+), CD15(dim+), CD64(variable+), CD14(weak+), CD4(dim+), CD56(variable+), CD7(weak+), CD11c(+), CD65(dim+), CD9(-), and MPO(+) suggesting acute myeloid leukemia. This particular pattern with a t(8;21) is seen in 15-18% of AML cases. Although it's in the favorable risk stratification category (NCCN Clinical Practice Guidelines 2023), the presence of complex abnormalities, including 1q+, deletion of 12p, and a der(12;22), suggests genomic instability and poor prognosis. The patient died six months post-transplant.
Acute myeloid leukemia (AML) is a heterogeneous disease, characterized by clonal expansion of undifferentiated myeloid precursors, leading to alterations in hematopoiesis and bone marrow failure. Characteristic chromosomal abnormalities in AML are translocations t(8;21), inv(16), t(15;17), t(9;22), as well as mutations of genes that regulate proliferation and survival (FLT 3, PTPN 11, ETV 6/PDGFB), or genes responsible for differentiation and apoptosis (RUNX-1/RUNX1T1, PML/RARA, KMT2A, CEBPA and CBFB). Amplification of RUNX1 is a rare event in AML. Herein we described a 60-year-old patient that was admitted to the hospital due to a clinical picture of symptoms of acute anemia, thrombocytopenia, leukocytosis, and profuse nasal bleeding, hepatomegaly, splenomegaly, and gallstones. The blood cell count indicated the presence of 72% blasts. The bone marrow also showed 97% of blasts of myeloid lineage. The flow cytometry study also showed findings compatible with AML (MPOneg/+, CD34+, CD19neg /+d, CD117+, CD38neg /+, HLA-DR ++, CD13neg /+, CD33neg, CD15neg, D56neg, CD123+, CD7neg, CD11bneg, CD64neg, CD41aneg, which represented 68% of the pathological cellularity). Chromosome analysis showed additional copies of an isochromosome 21q. FISH studies revealed five copies of RUNX1. Amplification of RUNX1 is a rare event in AML with only a few cases reported in the literature (mainly therapy related AML) and it is usually associated with poor prognosis.