OBJECTIVE: To analyze the clinical characteristics of patients with 11q23 rearrangement acute lymphoblastic leukemia (ALL) with non-KMT2A::AFF1 fusion genes. METHODS: The clinical data of 10 patients with KMT2A fusion gene positive and partner gene non-AFF1 ALL admitted to Henan Cancer Hospital from December 2016 to December 2024 were retrospectively summarized. The immunophenotype, molecular genetic characteristics, clinical manifestations and disease prognosis of these patients were analyzed. This research has been approved by the Medical Ethics Committee of Henan Cancer Hospital (Ethics No.: 2019342). RESULTS: Among the 10 patients, the fusion genes were KMT2A::MLLT1 in 7 cases, KMT2A::MLLT4, KMT2A::MLLT3 and KMT2A::MLLT10 in 1 case each. The European Group for the Immunological Classification of Leukemias (EGIL) classification included 6 cases of T-ALL, 2 cases of pro-B-ALL, 1 case of Common-B-ALL and 1 case of pre-B-ALL. 4 cases of B-ALL all expressed CD19, cCD79a, CD38 and HLA-DR, and some expressed CD34 and CD22, without expression or weak expression of CD10, without expression of CD20. One case was accompanied by myeloid marker CD15 expression. 6 cases of T-ALL all expressed CD34, CD7, most expressed CD38, and some expressed CD3, CD5, CD2, CD4 and CD8, and 1 case expressed CD4 and CD8 together. Chromosomal abnormalities were detected in 3 cases, 5 cases were positive for WT1 fusion gene, and 6 cases had gene alterations. 9 patients achieved the first complete remission (CR1) during chemotherapy, and 1 patient relapsed within 6 months after CR1. At the last follow up, 1 patient (the fusion gene was KMT2A::MLLT4) remained unrelieved. There were 2 cases of KMT2A rearrangement (KMT2A-r) persistent positive (+/+) and 8 cases of KMT2A-r negative (+/-). The overall survival (OS) rate and leukemia-free survival (LFS) rate of patients with KMT2A-r persistent positive were significantly lower than those of patients with negative change, and the differences were statistically significant (P values were all < 0.05). Among the 3 patients who received chemotherapy+allogeneic hematopoietic stem cell transplantation (allo-HSCT), no relapse was observed until the follow up day. The OS rate and LFS rate of patients with KMT2A::MLLT1 and chemotherapy+allo-HSCT were higher than those of non-KMT2A::MLLT1 and single chemotherapy patients, and the differences were not statistically significant (P values were all ≥ 0.05). There was no significant difference in OS rate and LFS rate between T-ALL and B-ALL patients (P values were all ≥ 0.05). The median LFS time of the 10 patients was 32 (0 ~ 100) months, and the median OS time was 36 (1 ~ 101) months. CONCLUSION The 11q23 rearrangement ALL with non-KMT2A::AFF1 transcript is mainly KMT2A::MLLT1, T-ALL is more common, and the rate of chromosomal karyotype detection is relatively low. Persistent positive KMT2A-r is unfavorable for patient survival, and allo-HSCT during the CR1 period may improve patient survival.
Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Female ; Male ; Myeloid-Lymphoid Leukemia Protein/genetics* ; Histone-Lysine N-Methyltransferase/genetics* ; Adult ; Adolescent ; Chromosomes, Human, Pair 11/genetics* ; Child ; Transcriptional Elongation Factors/genetics* ; Gene Rearrangement ; Oncogene Proteins, Fusion/genetics* ; Retrospective Studies ; Young Adult ; Middle Aged ; Prognosis ; Child, Preschool ; DNA-Binding Proteins/genetics*

OBJECTIVE: To explore the genetic characteristics of a Chinese pedigree with rare mosaic 11q partial duplication and its pathogenetic mechanisms. METHODS: A pedigree which underwent prenatal diagnosis at Wenzhou Central Hospital between September 25, 2015 and November 30, 2023 was selected for the study. Clinical data were collected from the pedigree. Peripheral blood samples from the parents, amniotic fluid from the fetus, and peripheral blood sample from the neonate were obtained. Genetic testing was carried out by using G-banded chromosomal karyotyping and single nucleotide polymorphism array (SNP-array) technology. Relevant literature was searched in the CNKI, Wanfang Data Knowledge Service Platform, and PubMed databases to summarize the clinical phenotypes of patients with 11q partial duplication. This study was approved by the Medical Ethics Committee of Wenzhou Central Hospital (Ethics No. L2024-07-080). RESULTS: The pregnant woman (G₃) had a history of adverse pregnancy outcomes. During her first pregnancy (G₁), prenatal ultrasound indicated intrauterine growth restriction and a Dandy-Walker variant. Follow-up at 8 years of age showed developmental delays and mild intellectual disability. During her second pregnancy (G₂), prenatal ultrasound revealed nasal bone hypoplasia, and the pregnancy was terminated at 23rd gestational week. During her third pregnancy (G₃), all prenatal tests were normal, and the neonate showed normal growth and development at 4 months of age. The karyotype of amniotic fluid of her first pregnancy was 46,X?, and the SNP-array analysis of neonatal peripheral blood showed arr[GRCh37/hg19]11q13.4q25(70432450_134607121)×2~3, with a mosaicism rate being approximately 40%. The karyotype for her second pregnancy was 46,X?,rec(11)dup(11q)inv(11)(p15q13)dmat[6]/46,X?[27], and the SNP-array result was arr[GRCh38]11q13.4q25(71406636_135067522)×2~3, with a mosaicism rate being approximately 75%. The karyotype for her third pregnancy was 46,X?,inv(11)(p15q13)mat, and the SNP-array result was arr(XN)×1,(1~22)×2. The karyotype of the woman was 46,XX,inv(11)(p15q13), and that of her husband was 46,XY. A review of 12 similar cases (including G₁) from the literature revealed that the common clinical phenotypes of 11q partial duplication included intellectual disability (12/12), developmental delay (12/12), ear abnormalities (12/12), microcephaly (10/12), seizures (8/12), hypotonia (8/12), and congenital heart malformations (7/12). CONCLUSION Mosaic partial duplication of 11q may underlie the genetic etiology of this pedigree. The pregnant woman is a carrier of an inversion on chromosome 11, which might have formed the mosaic 11q partial duplication through meiotic errors and mitotic trisomy rescue mechanisms during reproduction.
Adult ; Female ; Humans ; Male ; Pregnancy ; China ; Chromosome Duplication ; Chromosomes, Human, Pair 11/genetics* ; East Asian People/genetics* ; Karyotyping ; Mosaicism ; Pedigree ; Polymorphism, Single Nucleotide ; Prenatal Diagnosis

Objective: To explore the clinical, pathological, diagnostic, treatment, and prognostic features of children with mature B-cell lymphoma (MBCL) . Methods: This retrospective study included pediatric patients with MBCL with chromosome 11 long-arm abnormalities who were diagnosed and treated at our hospital from December 2018 to February 2023. Results: Among the 11 pediatric patients with MBCL, nine were male and two were female, with a median age of 9 (2-13) years and a median disease course of 1.8 (0.5-24) months. The clinical manifestations were cervical lymph node enlargement in four patients, nasal congestion and snoring in four patients, abdominal pain in two patients, and difficulty breathing in one patient. There were seven cases of Burkitt's lymphoma, two of follicular lymphoma, and two of advanced B-cell lymphoma according to the pathological morphology examination. No patients had central nervous system or bone marrow involvement, and no extensive metastasis was observed on B-ultrasound or positron emission tomography-computed tomography (PET/CT). One patient had a huge tumor lesion. The Revised International Pediatric Non-Hodgkin Lymphoma Staging System classified four patients as stage Ⅱ, five as stage Ⅲ, and two as stage Ⅳ. 11q probe detection showed five cases of 11q gain, three of 11q loss, and three of both gain and loss. FISH showed positive MYC expression in three patients, including eight with advanced B-cell lymphoma with 11q abnormalities and three with Burkitt's lymphoma with 11q abnormalities. According to the 2019 edition of the National Health Commission's diagnostic and treatment guidelines for invasive MBCL in children, one patient was classified as Group A, two as Group B, and eight as Group C. Early evaluation of the efficacy showed complete remission. After mid-term evaluation, the intensity of chemotherapy was reduced in Group B and Group C. Among two cases of chemotherapy, the remaining nine cases had a median follow-up of 32 (6-45) months, and none had event-related survival. Conclusion: The incidence of MBCL with 11q abnormalities in children is low, clinical symptoms are mild, and progression is slow. The absence of MYC, BCL2, BCL6 rearrangements, C-MYC negative and 11q abnormalities on FISH is an important diagnostic indicator, and reducing the intensity of chemotherapy can improve prognosis.
Humans ; Female ; Male ; Child ; Adolescent ; Burkitt Lymphoma/genetics* ; Chromosomes, Human, Pair 11 ; Positron Emission Tomography Computed Tomography ; Retrospective Studies ; Lymphoma, Follicular ; Chromosome Aberrations

OBJECTIVE: To assess the value of detecting the rearrangement of mixed lineage leukemia (MLL) gene in children with acute mononuclear leukemia (AML). METHODS: Dual-color fluorescence in situ hybridization (FISH) probe was used to detect MLL gene rearrangement in 68 children with AML by interphase FISH. The results were compared with that of conventional G banding chromosomal analysis. RESULTS: Among the 68 children, 28 were detected by FISH with positive hybridization signals, with a detection rate for MLL gene rearrangement being 41.2%. Twelve (17.6%) reciprocal translocations and interruption of 11q23 were detected by G banding analysis. The difference in the detection rates between the two methods was statistically significant (P< 0.05). CONCLUSION The sensitivity of FISH assay for MLL gene rearrangement was significantly higher than that of G banding chromosomal karyotyping. Combined use of both methods for children with AML can improve the detection rate of MLL gene rearrangements and provide crucial clues for clinical diagnosis, treatment and prognosis.
Child ; Chromosomes, Human, Pair 11 ; Gene Rearrangement ; Histone-Lysine N-Methyltransferase ; genetics ; Humans ; In Situ Hybridization, Fluorescence ; Leukemia, Monocytic, Acute ; genetics ; Myeloid-Lymphoid Leukemia Protein ; genetics ; Translocation, Genetic

OBJECTIVETo report on a case of therapy-related acute monocytic leukemia(t-AML) with t(11;17) (q23;q21)/MLL-AF17q after successful treatment for acute promyelocytic leukemia(APL) with t(15;17) (q22;q21)/PML-RARα.

METHODSA MICM method (bone marrow morphology(M), immunophenotype(I), cytogenetics(C), and molecular biology(M)) was used for the diagnosis and classification of the disease at the time of onset and transformation.

RESULTSThe patient was initially identified with typical morphology and immunophenotype of APL. She has carried t(15;17)(q22;q21) and PML-RARα fusion gene but was without t(11;17)(q23;q21) or MLL gene abnormalities. After 13 months of successful treatment, she has transformed to AML with typical morphology and immunophenotype. t(11;17)(q23;q21) and MLL-AF17q fusion gene were detected in her bone marrow sample, while no PLZF-RARα fusion gene was detected by real-time quantitative reverse-transcription PCR(RQ-PCR) and fluorescence in situ hybridization(FISH).

CONCLUSIONt-AML is a serious complication after successful treatment of APL. t(11;17)(q23;q21) is not specific for the diagnosis of variant APL and can also be detected in t-AML. RQ-PCR and FISH are essential for the diagnosis of such patients.

Chromosomes, Human, Pair 11 ; Chromosomes, Human, Pair 15 ; Chromosomes, Human, Pair 17 ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Leukemia, Monocytic, Acute ; genetics ; Leukemia, Promyelocytic, Acute ; genetics ; Middle Aged ; Neoplasms, Second Primary ; genetics

OBJECTIVETo explore the genetic cause for two children with omphalocele.

METHODSThe patients were examined, and the medical history of their families was collected. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) was performed to detect potential mutation in the patients.

RESULTSLoss of methylation of imprinting center 2 (IC2) at the 11p15.5 region of the maternal chromosome was detected in both children.

CONCLUSIONThe two patients were diagnosed with Beckwith-Wiedemann syndrome by MS-MLPA. The loss of methylation of IC2 probably underlies the disease in both patients.

Beckwith-Wiedemann Syndrome ; genetics ; Chromosomes, Human, Pair 11 ; DNA Methylation ; Female ; Genomic Imprinting ; Humans ; Infant ; Infant, Newborn ; Male ; Multiplex Polymerase Chain Reaction

OBJECTIVETo carry out genetic analysis for a fetus with Dandy-Walker malformation and provide prenatal diagnosis for its parents during the subsequent pregnancy.

METHODSRoutine G-banding was carried out to analyze the karyotype of the fetus and its parents, and next-generation sequencing (NGS) and fluorescence in situ hybridization (FISH) were used to verify the result.

RESULTSThe father showed a normal karyotype, while the mother was found to carry a balanced t(11; 22) (q23; q11) translocation. NGS and FISH analysis verified that the supernumerary marker chromosome carried by the fetus was der(22) t(11; 22) (q23;q11). The fetus was diagnosed with Emanuel syndrome. During the next pregnancy, the fetus was found to carry the same balanced translocation as its mother. After genetic counseling, the couple decided to continue with the pregnancy, and eventually delivered a healthy baby.

CONCLUSIONA fetal case of Emanuel syndrome has been identified. The derivative der(22) t(11; 22)(q23; q11) chromosome probably underlies the Dandy-Walker malformation in the fetus. Combined cytogenetic and molecular analyses can attain a more precise diagnosis for fetal abnormalities detected by ultrasonography.

Adult ; Chromosome Disorders ; diagnosis ; genetics ; Chromosomes, Human, Pair 11 ; Chromosomes, Human, Pair 22 ; Cleft Palate ; diagnosis ; genetics ; Female ; Follow-Up Studies ; Heart Defects, Congenital ; diagnosis ; genetics ; Humans ; Intellectual Disability ; diagnosis ; genetics ; Muscle Hypotonia ; diagnosis ; genetics ; Pregnancy ; Prenatal Diagnosis ; Translocation, Genetic

OBJECTIVETo investigate the prenatal application of single nucleotide polymorphism array (SNP array) in the identification of 5p deletion syndrome with partial trisomy 11q.

METHODSG-banded karyotyping and SNP array were performed using amniocytes on a fetus with multiple malformations for the identification of chromosome abnormality. Furthermore, karyotyping was carried out on the parental peripheral blood specimens to ascertain the origin of chromosome abnormalities and then fluorescence in situ hybridization (FISH) was also utilized to confirm the results.

RESULTSKaryotype of amniocyte showed 46, XY, der(5) (?::p15 → qter). SNP array revealed a 13.907 Mb deletion at 5p15.33p15.2 (chr5: 113576-14020561), overlapping the region of 5p deletion syndrome, and a 18.254 Mb duplication at 11q23.3 q25 (chr11: 116684627-134938470), overlapping no known syndrome. Karyotype of the parents showed a normal 46,XX in mother and 46,XY,t(5;11)(p15;q23) in father. Three-color metaphase FISH analysis on paternal peripheral blood specimens also confirmed the paternal karyotyping result.

CONCLUSIONSNP array could uncover 5p deletion syndrome with partial trisomy 11q unidentified by G-banded karyotyping and accurately locate the genomic breakpoints, facilitating the mapping of pathogenic critical regions and the identification of candidate genes, also accumulating research data for genotype-phenotype study.

Adult ; Chromosome Banding ; Chromosome Deletion ; Chromosome Disorders ; diagnosis ; embryology ; genetics ; Chromosomes, Human, Pair 11 ; genetics ; Chromosomes, Human, Pair 5 ; genetics ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Male ; Oligonucleotide Array Sequence Analysis ; methods ; Polymorphism, Single Nucleotide ; Pregnancy ; Prenatal Diagnosis ; methods ; Trisomy ; diagnosis ; genetics

No abstract available.
Base Sequence ; Cell Cycle Proteins/*genetics ; Chromosomes, Human, Pair 11 ; Chromosomes, Human, Pair 22 ; Female ; Gene Rearrangement ; Histone-Lysine N-Methyltransferase/*genetics ; Humans ; Immunophenotyping ; In Situ Hybridization, Fluorescence ; Karyotype ; Leukemia, Myeloid, Acute/*diagnosis/metabolism ; Male ; Myeloid-Lymphoid Leukemia Protein/*genetics ; Oncogene Proteins, Fusion/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Septins/*genetics ; Sequence Analysis, DNA ; Translocation, Genetic ; Young Adult

OBJECTIVETo study the clinical features and diagnosis of 7 patients with atypical mantle cell lymphoma (MCL).

METHODSThe 7 MCL patients were misdiagnosed as chronic lymphocytic leukemia (CLL) due to a score of 4 for their immunophenotypes. The clinical features and diagnosis of such patients were retrospectively analyzed.

RESULTSSix patients had superficial lymphadenectasis but their lymph nodes could not be palpated. All 7 patients were as stage IV considering bone marrow infiltration. Scores of immunophenotype of CLL were 4, and interphase fluorescence in situ hybridization (FISH) for t(11;14) were positive in all patients.

CONCLUSIONSome MCL patients have clinical features similar to CLL. Interphase FISH can play an important role in the diagnosis of MCL.

Aged ; Chromosomes, Human, Pair 11 ; genetics ; Chromosomes, Human, Pair 14 ; genetics ; Female ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Lymphoma, Mantle-Cell ; diagnosis ; genetics ; Male ; Middle Aged ; Translocation, Genetic