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inv(16)(p13q22) CBFB::MYH11

t(16;16)(p13;q22) CBFB::MYH11

del(16)(q22) CBFB::MYH11

Written1999-06Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
This article is an update of :
1997-11Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

(Note : for Links provided by Atlas : click)


ICD-Morpho 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
ICD-Morpho 9871/3 AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11
ICD-Morpho 9920/3 Therapy-related myeloid neoplasms
ICD-Morpho 9975/3 Chronic myelogenous leukaemia, BCR-ABL1 positive; Myeloproliferative neoplasm, unclassifiable; Myelodysplastic/myeloproliferative neoplasm, unclassifiable
ICD-Morpho 9989/3 Myelodysplastic syndrome, unclassifiable
Atlas_Id 1036
Note the three chromosome anomalies are variants of each other, and they share identical clinical features and genetic pathogenesis
  TOP: inv(16)(p13q22) G- banding (left) - Courtesy Jean-Luc Lai and Alain Vanderhaegen; R- banding center bottom: - Courtesy Christiane Charrin, center top and FISH (middle right) - Courtesy Pascale Cornillet-Lefebvre and Stephanie Struski; FISH (right) - Courtesy Hossein Mossafa; commercial FISH probes, split in the inv(16). BOTTOM: t(16;16)(p13;q22) G-banding - left two - Courtesy Diane H. Norback, Eric B. Johnson, and Sara Morrison-Delap, UW Cytogenetic Services; middle two and FSIH Vysis LSI CBFB Dual Color, Break Apart Rearrangement Probe ?nuc ish(CBFBx2)(5'CBFB sep 3'CBFBx1) - Courtesy Ian Brooks and Jackie Challis, Oncology Cytogenetics, Victorian Clinical Genetics Services, Australia.

Clinics and Pathology

Disease acute non lymphoblastic leukaemia (AML); myelodysplastic syndromes (MDS) at times
Phenotype / cell stem origin nearly pathognomonic of M4eo-AML (all M4eo share the 16q22 anomaly -see also below-, but not all 16p13/16q22 are found in the M4eo subtype: i.e. this anomaly, although mainly found in M4-AML with marked eosinophilia, may (rarely) been found in : M2 or M5, M4 without eo, or in MDS; there are also known cases of chronic myelogenous leukaemia in blast crisis (BC-CML) with a M4 eo phenotype and inv(16); found at times in treatment related AML; 3 cases of infant leukaemia so far described; note: CD2 (T-cell marker) may be co-expressed
Epidemiology 5-10% of AML, 20% of M4
Clinics CNS involvement is frequent, according to some authors, in particular at relapse
Cytology most often: eosinophils > 5%, with large immature basophilic granules, NASCA+, in the bone marrow (but normal in blood: this M4 do not show the 'eo' characteristic in blood)
Patients with inv(16) usually correspond to the subclass of AML M4, with a specific abnormal eosinophil component and is considered as a distinct entity in correlation with these specific chromosomal abnormalities. These cases of AML M4 are referred as AML M4EO. In addition to the morphological features of AML M4 excess of monocytes), the bone marrow shows a variable number of eosinophils at all stages of maturation without significant maturation arrest. The most striking abnormalities involve the immature eosinophilic granules. Those are mainly evident at the promyelocyte and myelocyte stages. The abnormalities are not usually evident at later stages of maturation. These eosinophilic granules are often larger than those normally seen in immature eosinophils, purple-violet in color and in some cells are so dense that they obscure the cell morphology - Text and iconography Courtesy Georges Flandrin 2001.
Prognosis high CR rate; better prognosis than most other AML; median survival may be 5yrs


Cytogenetics Morphological may be overlooked, especially with R-banding; best seen without banding procedure ('giemsa') for some workers
Cytogenetics Molecular with 16p13 probes : as a deletion within 16p13 often accompany the 16p13/16q22 rearrangement (in 20% of cases), the split signal may be lost
Additional anomalies none 2/3 of cases; +8, +22 in 15% each, del(7q), +2; apparently without prognostic significance
Variants are known:
1- t(16;16)(p13;q22);
- del(16)(q22): may be associated with less typical phenotype and preceding MDS, older age, complex karyotype, worse prognosis;

2- but also: translocations of 16q22 with various partners in: t(1;16)(p31-32;q22), t(3;16)(q21;q22), t(5;16)(q33;q22), associated with eosinophils anomalies

Genes involved and Proteins

Gene NameMYH11 (myosin heavy chain) (incomplete)
Location 16p13.11
  c-MYH11 (16p13) in normal cells: PAC 1032E3 (top) and PAC 1179J13 (below) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
Protein contains a N-term ATPase head responsible for actin binding and mechanical movement, and a C-term long repeat of coil-coil domain to facilitate filament aggregates; member of the myosin II family
Gene NameCBFB (subunit b of core binding factor)
Location 16q22.1
Protein subunit of the transcription factor complex CBF; CBFb by itself does not contain any DNA binding motif or transcriptional activation domain, but forms a dimer with CBFa: --> transcription factor

Result of the chromosomal anomaly

Hybrid gene
Description 5' CBFb - 3' MYH11; breakpoint in CBFB intron n° 5 and in MYH11 intron A (i.e. : 5)
Transcript at least 8 different CBFb-MYH11 fusion transcripts have been described, transcript type A (with positions at nucleotides 495 and 1921 respectively) being found in about 90% of the patients;most braekpoints in MYH11 are also clustered; no reciprocal MYH11-CBFB transcript
Fusion Protein
Description N-term - the first 165 (or 133 in a few cases) amino acids of CBFb, removing only 17 or 22 amino acids fused to the tail of MYH11 C-term with its multimerization domain; also variable breakpoint in MYH11; identical fusion protein in the cases of RAEBT and BC-CML
Expression Localisation nuclear localisation
Oncogenesis the fusion protein seems both to diminuish the quantity of active CBF and to compete with it, there is accumulation of CBFb-MYH11/CBFa multimeres in the nucleus

To be noted

Case Report Insertion as an alternative mechanism of CBFB-MYH11 gene fusion in a new case of acute myeloid leukemia with an abnormal chromosome 16


Acute nonlymphocytic leukemia with marrow eosinophilia and chromosome 16 abnormality: a report of 18 cases.
Bernard P, Dachary D, Reiffers J, Marit G, Wen Z, Jonveaux P, David B, Lacombe F, Broustet A
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1989 ; 3 (10) : 740-745.
PMID 2779289
Abnormalities of chromosome 16q in myeloid malignancy: 14 new cases and a review of the literature.
Betts DR, Rohatiner AZ, Evans ML, Rassam SM, Lister TA, Gibbons B
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1992 ; 6 (12) : 1250-1256.
PMID 1453770
Chromosome 16 abnormalities associated with myeloid malignancies.
Campbell LJ, Challis J, Fok T, Garson OM
Genes, chromosomes & cancer. 1991 ; 3 (1) : 55-61.
PMID 2069909
Cloning the breakpoint cluster region of the inv(16) in acute nonlymphocytic leukemia M4 Eo.
Dauwerse JG, Wessels JW, Giles RH, Wiegant J, van der Reijden BA, Fugazza G, Jumelet EA, Smit E, Baas F, Raap AK
Human molecular genetics. 1993 ; 2 (10) : 1527-1534.
PMID 8268905
Identification of yeast artificial chromosomes containing the inversion 16 p-arm breakpoint associated with acute myelomonocytic leukemia.
Liu P, Claxton DF, Marlton P, Hajra A, Siciliano J, Freedman M, Chandrasekharappa SC, Yanagisawa K, Stallings RL, Collins FS
Blood. 1993 ; 82 (3) : 716-721.
PMID 8338941
Molecular pathogenesis of the chromosome 16 inversion in the M4Eo subtype of acute myeloid leukemia.
Liu PP, Hajra A, Wijmenga C, Collins FS
Blood. 1995 ; 85 (9) : 2289-2302.
PMID 7727763
Heterogeneity in CBF beta/MYH11 fusion messages encoded by the inv(16)(p13q22) and the t(16;16)(p13;q22) in acute myelogenous leukemia.
Shurtleff SA, Meyers S, Hiebert SW, Raimondi SC, Head DR, Willman CL, Wolman S, Slovak ML, Carroll AJ, Behm F
Blood. 1995 ; 85 (12) : 3695-3703.
PMID 7780153
Genomic acute myeloid leukemia-associated inv(16)(p13q22) breakpoints are tightly clustered.
van der Reijden BA, Dauwerse HG, Giles RH, Jagmohan-Changur S, Wijmenga C, Liu PP, Smit B, Wessels HW, Beverstock GC, Jotterand-Bellomo M, Martinet D, Mühlematter D, Lafage-Pochitaloff M, Gabert J, Reiffers J, Bilhou-Nabera C, van Ommen GJ, Hagemeijer A, Breuning MH
Oncogene. 1999 ; 18 (2) : 543-550.
PMID 9927211


This paper should be referenced as such :
Huret, JL
inv(16)(p13q22) - t(16;16)(p13;q22) - del(16)(q22)
Atlas Genet Cytogenet Oncol Haematol. 1999;3(3):147-149.
Free journal version : [ pdf ]   [ DOI ]
On line version :
History of this paper:
Huret, JL. inv(16)(p13q22). Atlas Genet Cytogenet Oncol Haematol. 1997;1(2):85-86.

Other genes implicated (Data extracted from papers in the Atlas) [ 8 ]


Translocations implicated (Data extracted from papers in the Atlas)

 del(16)(q22) CBFB/MYH11
 inv(16)(p13q22) CBFB/MYH11
 t(16;16)(p13;q22) CBFB/MYH11

External links

CBFB (16q22.1) MYH11 (16p13.11)

CBFB (16q22.1) MYH11 (16p13.11)

Mitelman databasedel(16)(q22)
Mitelman databaseinv(16)(p13q22)
Mitelman databaset(16;16)(p13;q22)
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9861/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9871/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9920/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9975/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9989/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
Mitelman databaseCBFB::MYH11 [MCList]  CBFB (16q22.1) MYH11 (16p13.11)
Other databaseinv(16) involving CBFB and MYH11 genes (Bari)
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed

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