inv(16)(p13q22) CBFB/MYH11 in treatment related leukemia

2003-10-01   Jean-Loup Huret  

1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Clinics and Pathology

Disease

Treatment related myelodysplasia (t-MDS) or acute myeloid leukaemias (t-AML)

Note

The study included 48 cases; t-MDS without progression to AML accounted for 8%, t-MDS with progression to AML for 13% and t-AML for the remaining 79% the AML subtype was M4eo in 83%, M2 in 14%; no case of acute lymphoblastic leukaemia

Epidemiology

inv(16)(p13q22) was found in 9% of t-MDS/t-AML; sex ratio: 18M/30F

Clinics

Age at diagnosis of the primary disease 43 yrs (range 6-75); age at diagnosis of the t-MDS/t-AML: 48 yrs (range 13-77). Median interval was short: 22 mths (range: 8-533). Primary disease was a solid tumor in 71% of cases (in particular breast cancer, sarcoma, cancer of the ovary) and a hematologic malignancy in 27%, treatment was radiotherapy (21%, a relatively high proportion compared to other groups), chemotherapy (29%), or both (50%). Treatment included topoisomerase II inhibitors in 60% of cases and alkylating agents in 63%.

Prognosis

Patients under 55 yrs of age had better outcome. Median survival was 29 mths, with 45% of patients surviving at 5 yrs, the best survival among subgroups of treatment related leukemias with a balanced chromosome aberration (patients with 11q23 rearrangement, 3q21q26 rearrangement, 12p13 rearrangement, t(9;22), t(8;16), or a 21q22 rearangement)). Patients with t(15;17) had similar median survival, but less long term survivors.

Result of the Chromosomal Anomaly

Description

5CBFB -3¹ MYH11

Highly cited references

Pubmed IDYearTitleCitations
318179112019Core Binding Factor Leukemia: Chromatin Remodeling Moves Towards Oncogenic Transcription.150
344401572021How to Improve Prognostication in Acute Myeloid Leukemia with CBFB-MYH11 Fusion Transcript: Focus on the Role of Molecular Measurable Residual Disease (MRD) Monitoring.123
380610172023Proteogenomic analysis reveals cytoplasmic sequestration of RUNX1 by the acute myeloid leukemia-initiating CBFB::MYH11 oncofusion protein.112
328312962020CBFB-MYH11 fusion neoantigen enables T cell recognition and killing of acute myeloid leukemia.93
368743782023Therapy-related core binding factor acute myeloid leukemia.86
297559562018Preleukemia and Leukemia-Initiating Cell Activity in inv(16) Acute Myeloid Leukemia.81
348044412021Gastrointestinal Myeloid Sarcoma a Case Presentation and Review of the Literature.80
277986252016The genomic landscape of core-binding factor acute myeloid leukemias.79
370199722023Etiology of oncogenic fusions in 5,190 childhood cancers and its clinical and therapeutic implication.71
346866642021Targeting miR-126 in inv(16) acute myeloid leukemia inhibits leukemia development and leukemia stem cell maintenance.70
343368312021CBFB-MYH11 Fusion Sequesters RUNX1 in Cytoplasm to Prevent DNMT3A Recruitment to Target Genes in AML.67
205897202010RUNX1 repression-independent mechanisms of leukemogenesis by fusion genes CBFB-MYH11 and AML1-ETO (RUNX1-RUNX1T1).57
359739832022Phenotypically-defined stages of leukemia arrest predict main driver mutations subgroups, and outcome in acute myeloid leukemia.52
171854622007CBFB-MYH11 hinders early T-cell development and induces massive cell death in the thymus.50
221603782012KIT with D816 mutations cooperates with CBFB-MYH11 for leukemogenesis in mice.50
360112782022PPP1R7 Is a Novel Translocation Partner of CBFB via t(2;16)(q37;q22) in Acute Myeloid Leukemia.49
200075442010Cbfb/Runx1 repression-independent blockage of differentiation and accumulation of Csf2rb-expressing cells by Cbfb-MYH11.48
364420872022Transcriptome-based molecular subtypes and differentiation hierarchies improve the classification framework of acute myeloid leukemia.47
329294732020RUNX1 and CBFβ-SMMHC transactivate target genes together in abnormal myeloid progenitors for leukemia development.47
316243762020Gata2 deficiency delays leukemogenesis while contributing to aggressive leukemia phenotype in Cbfb-MYH11 knockin mice.46
150446902004Identification of genes that synergize with Cbfb-MYH11 in the pathogenesis of acute myeloid leukemia.44
307420532019IL1RL1 is dynamically expressed on Cbfb-MYH11(+) leukemia stem cells and promotes cell survival.43
347715192021CBFB Break-Apart FISH Testing: An Analysis of 1629 AML Cases with a Focus on Atypical Findings and Their Implications in Clinical Diagnosis and Management.42
290180802017Chd7 deficiency delays leukemogenesis in mice induced by Cbfb-MYH11.41
318967822020The clinical mutatome of core binding factor leukemia.40
280307952017AML associated oncofusion proteins PML-RARA, AML1-ETO and CBFB-MYH11 target RUNX/ETS-factor binding sites to modulate H3ac levels and drive leukemogenesis.40
364523492022Analytical study of RUNX1-RUNXT1, PML-RARA, CBFB-MYH11, BCR-ABL1(p210) , and KMT2-MLLT3 in Mexican children with acute myeloid leukemia: A multicenter study of the Mexican interinstitutional group for the identification of the causes of childhood leukemia (MIGICCL).39
216385192011CBFB and MYH11 in inv(16)(p13q22) of acute myeloid leukemia displaying close spatial proximity in interphase nuclei of human hematopoietic stem cells.39
384279242024Targeting Molecular Measurable Residual Disease and Low-Blast Relapse in AML With Venetoclax and Low-Dose Cytarabine: A Prospective Phase II Study (VALDAC).37
357945672022Molecular dissection of a hyper-aggressive CBFB-MYH11/FLT3-ITD-positive acute myeloid leukemia.37
345477722021CBFB-MYH11 fusion transcripts distinguish acute myeloid leukemias with distinct molecular landscapes and outcomes.35
257427482015Runx1 is required for hematopoietic defects and leukemogenesis in Cbfb-MYH11 knock-in mice.34
384932002024Application of droplet digital PCR in minimal residual disease monitoring of rare fusion transcripts and mutations in haematological malignancies.34
318997992020Prospective evaluation of prognostic impact of KIT mutations on acute myeloid leukemia with RUNX1-RUNX1T1 and CBFB-MYH11.33
252662202014CBFB-MYH11 hypomethylation signature and PBX3 differential methylation revealed by targeted bisulfite sequencing in patients with acute myeloid leukemia.33
354455942022Comprehensive Mutation Profile in Acute Myeloid Leukemia Patients with RUNX1-RUNX1T1 or CBFB-MYH11 Fusions.31
354979382022Therapy-related acute myeloid leukemia: A case series.30
332049992020Identification of Fusion Gene Breakpoints is Feasible and Facilitates Accurate Sensitive Minimal Residual Disease Monitoring on Genomic Level in Patients With PML-RARA, CBFB-MYH11, and RUNX1-RUNX1T1.15
372259652023Characterization of leukemia progression in the Cbfb-MYH11 knockin mice by single cell RNA sequencing.14
338161052021Primary peritoneal myeloid sarcoma in association with CBFB/MYH11 fusion.13
232365512013Acute myeloid leukemia with cryptic CBFB-MYH11 type D.10
345129852021Abnormal eosinophils with immature eosinophilic granules in chronic myeloid leukemia in accelerated phase.2
381537682023CBFB::MYH11 fusion in a nonmonocytic acute myeloid leukemia.0
115611562001Function of the inv(16) fusion gene CBFB-MYH11.0
341837802021Prognostic values of D816V KIT mutation and peri-transplant CBFB-MYH11 MRD monitoring on acute myeloid leukemia with CBFB-MYH11.0
316714342020Myeloid Sarcoma With CBFB-MYH11 Fusion (inv(16) or t(16;16)) Prevails in the Abdomen.0
289060042017Acute myeloid leukaemia (FAB AML-M4Eo) with cryptic insertion of cbfb resulting in cbfb-Myh11 fusion.0
383887942024Clinical implications of additional chromosomal abnormalities in adult acute myeloid leukemia with inv (16)/t(16;16)/CBFB::MYH11.0
366536962023Comprehensive molecular understanding of pediatric acute myeloid leukemia.0
322022502021Detection of del(16q) using the CBFB-MYH11 translocation dual fusion probe.0
313531652020Detection of a novel CBFB-MYH11 fusion transcript in acute myeloid leukemia M1 with inv(16)(p13q22).0
325884342021The loss or absence of minimal residual disease of <0·1% at any time after two cycles of consolidation chemotherapy in CBFB-MYH11-positive acute myeloid leukaemia indicates poor prognosis.0
112417872001Detection and quantification of CBFB/MYH11 fusion transcripts in patients with inv(16)-positive acute myeloblastic leukemia by real-time RT-PCR.0
351286342022TET2 deficiency cooperates with CBFB-MYH11 to induce acute myeloid leukaemia and represents an early leukaemogenic event.0
360390182022Mutual exclusivity between the fusion gene CBFB::MYH11 and somatic mitochondrial mutations in acute myeloid leukaemia.0
151561862004Mechanism of leukemogenesis by the inv(16) chimeric gene CBFB/PEBP2B-MHY11.0
205135352010Acute myeloid leukemia with inv(16) with CBFB-MYH11, 3'CBFB deletion, variant t(9;22) with BCR-ABL1, and del(7)(q22q32) in a pediatric patient: case report and literature review.0
220325822011Core-binding factor acute myeloid leukemia.0
282996582017Clinical Relevance of RUNX1 and CBFB Alterations in Acute Myeloid Leukemia and Other Hematological Disorders.0
89295371996Failure of embryonic hematopoiesis and lethal hemorrhages in mouse embryos heterozygous for a knocked-in leukemia gene CBFB-MYH11.0
309195052019Measurable residual disease testing for personalized treatment of acute myeloid leukemia.0
282996612017Molecular Basis and Targeted Inhibition of CBFβ-SMMHC Acute Myeloid Leukemia.0
87514661996The gene product of CBFB-MYH11.0
122391552002Role of Cbfb in hematopoiesis and perturbations resulting from expression of the leukemogenic fusion gene Cbfb-MYH11.0
85859601996Transforming properties of the leukemic inv(16) fusion gene CBFB-MYH11.0
77952331995RT-PCR diagnosis of patients with acute nonlymphocytic leukemia and inv(16)(p13q22) and identification of new alternative splicing in CBFB-MYH11 transcripts.0
317210362020Mature neutrophils with Auer rod bundles in CBFB-MYH11-positive acute myeloid leukemia.0
240025882014CBFB-MYH11/RUNX1 together with a compendium of hematopoietic regulators, chromatin modifiers and basal transcription factors occupies self-renewal genes in inv(16) acute myeloid leukemia.0
172878582007Rare CBFB-MYH11 fusion transcripts in AML with inv(16)/t(16;16) are associated with therapy-related AML M4eo, atypical cytomorphology, atypical immunophenotype, atypical additional chromosomal rearrangements and low white blood cell count: a study on 162 patients.0
300062582018Molecular Minimal Residual Disease Testing in Acute Myeloid Leukemia: A Review for the Practicing Clinician.0
388012262024Integrative immunophenotypic and genetic characterization of acute myeloid leukemia with CBFB rearrangement.0
192157882009Detection of a novel CBFB/MYH11 variant fusion transcript (K-type) showing partial insertion of exon 6 of CBFB gene using two commercially available multiplex RT-PCR kits.0
253488712015Prognosis and monitoring of core-binding factor acute myeloid leukemia: current and emerging factors.0
276505112018Monitoring of post-transplant CBFB-MYH11 as minimal residual disease, rather than KIT mutations, can predict relapse after allogeneic haematopoietic cell transplantation in adults with inv(16) acute myeloid leukaemia.0
256357582015Emerging diagnostic and therapeutic approaches in core binding factor acute myeloid leukaemia.0
212812262011De novo acute myeloid leukemia with Philadelphia chromosome (BCR-ABL) and inversion 16 (CBFB-MYH11): report of two cases and review of the literature.0
274688692016Incidence of preleukemic fusion genes in healthy subjects.0
75776151995Detection of CBFB/MYH11 transcripts in patients with inversion and other abnormalities of chromosome 16 at presentation and remission.0
170527532007Detection of the CBFB/MYH11 fusion gene in de novo acute myeloid leukemia (AML): a single-institution study of 224 Japanese AML patients.0
398035622024Loss of the Inv(16) Oncogene CBFB::MYH11 Eliminates Leukemia from the Blood and Spleen, but not the Bone Marrow.0
371023022023TP53 and RB1 alterations characterize poor prognostic subgroups in pediatric acute myeloid leukemia.0
356220052022AML with inv(16)/t(16;16) and high-risk cytogenetic abnormalities: atypical features and unfavorable outcome.0
386546582024Lower relapse incidence with haploidentical versus matched sibling or unrelated donor hematopoietic cell transplantation for core-binding factor AML patients in CR2: A study from the Global Committee and the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.0
121397242002Minimal residual disease quantification in patients with acute myeloid leukaemia and inv(16)/CBFB-MYH11 gene fusion.0
382201492023[Acute myeloid leukemia with type I CBFB::MYH11 fusion gene not detected by screening test for leukemia-related chimeric genes].0
331625102020[Clinical significance of MRD in AML].0
284754342017Enhancing acute myeloid leukemia therapy - monitoring response using residual disease testing as a guide to therapeutic decision-making.0
380845512023Therapy-related acute myeloid leukemia with CBFB/MYH11 in a patient with ovarian cancer after exposure to chemotherapy.0
86304301996Novel CBFB-MYH11 fusion transcripts or reverse transcription-polymerase chain reaction artifacts?0
127887912003Rapid identification of CBFB-MYH11-positive acute myeloid leukemia (AML) cases by one single MYH11 real-time RT-PCR.0
275127652016Wilms’ Tumor Gene (WT1) Expression and Minimal Residual Disease in Acute Myeloid Leukemia.0
165025842006Diagnosis and monitoring of CBFB-MYH11-positive acute myeloid leukemia by qualitative and quantitative RT-PCR.0
3518421720223'CBFB deletion in CBFB-rearranged acute myeloid leukemia retains morphological features associated with inv(16), but patients have higher risk of relapse and may require stem cell transplant.0
206251242010Prognostic impact of minimal residual disease in CBFB-MYH11-positive acute myeloid leukemia.0
313998072019BCR-ABL1- and CBFB-MYH11-positive chronic myeloid leukemia presenting with primary blast crisis and marrow fibrosis.0
161930882005Quantification of CBFB-MYH11 fusion gene levels in paired peripheral blood and bone marrow samples by real-time PCR.0
238781402013Exome sequencing identifies recurring FLT3 N676K mutations in core-binding factor leukemia.0
356135012022Jumping translocation involving chromosome 13q in a patient with Crohn's Disease and inv(16)(p13.1q22)/CBFB-MYH11 acute myeloid leukemia.0
199012612010Strikingly different molecular relapse kinetics in NPM1c, PML-RARA, RUNX1-RUNX1T1, and CBFB-MYH11 acute myeloid leukemias.0
295175042018Somatic Mutations and Intratumoral Heterogeneity of MYH11 Gene in Gastric and Colorectal Cancers.0

Article Bibliography

Pubmed IDLast YearTitleAuthors
119212732002Balanced chromosome abnormalities inv(16) and t(15;17) in therapy-related myelodysplastic syndromes and acute leukemia: report from an international workshop.Andersen MK et al

Summary

Fusion gene

CBFB/MYH11 CBFB (16q22.1) MYH11 (16p13.11) M ins(16)(q22p13p13) ins(16;16)(q22;p13p13) inv(16)(p13q22) t(16;16)(p13;q22)|CBFB/MYH11 CBFB (16q22.1) MYH11 (16p13.11) TIC

Note

This data is extracted from a very large study from an International Workshop on treatment related leukemias - restricted to balanced chromosome aberrations (i.e.: -5/del(5q)and -7/del(7q) not taken into account per see), published in Genes,Chromosomes and Cancer in 2002.
Atlas Image
inv(16)(p13q22) CBFB/MYH11  and t(16;16)(p13;q22) CBFB/MYH11 Top: inv(16) FISH and diagram - Courtesy Hossein Mossafa; Middle Left: first row: inv(16)(p13q22) G-banding - Courtesy Diane H. Norback, Eric B. Johnson, and Sara Morrison-Delap, UW Cytogenetic Services; second row - Courtesy Hossein Mossafa; Middle Right: t(16;16)(p13;q22) u2013 Courtesy Adriana Zamecnikova; Bottom: Fluorescence in situ hybridization with the Vysis LSI CBFB break apart probe (Abbott Molecular, US) showing disruption of the gene as a result of (A) inv(16) and (B) its translocation to der(16) as a result of t(16;16) u2013 Courtesy Adriana Zamecnikova - Courtesy Adriana Zamecnikova.

Citation

Jean-Loup Huret

inv(16)(p13q22) CBFB/MYH11 in treatment related leukemia

Atlas Genet Cytogenet Oncol Haematol. 2003-10-01

Online version: http://atlasgeneticsoncology.org/haematological/1297/inv(16)(p13q22)