Concurrent MPL515 and JAK2V617F mutations in myelofibrosis:: chronology of clonal emergence and changes in mutant allele burden over time

被引:78
作者
Lasho, Terra L.
Pardanani, Animesh
McClure, Rebecca F.
Mesa, Ruben A.
Levine, Ross L.
Gilliland, D. Gary
Tefferi, Ayalew
机构
[1] Mayo Clin, Div Hematol, Rochester, MN 55905 USA
[2] Dana Farber Canc Inst, Rochester, MN USA
[3] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA
[4] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA
关键词
myelofibrosis; MPLW515L; MPLW515K; essential thrombocythaemia;
D O I
10.1111/j.1365-2141.2006.06348.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
MPLW515L/K and JAK2V617F can co-exist in myelofibrosis with myeloid metaplasia (MMM). The chronology of clonal emergence was studied in three such cases using serially stored bone marrow. At diagnosis, a major MPL515 mutant clone was accompanied by a minor JAK2V617F clone in all three instances. At 25 time points over a period of 4-8 years, allele burden fluctuated but remained high for MPLW515L/K and low for JAK2V617F. We conclude that MPLW515L/K and JAK2V617F are both early events in MMM and allele burden, rather than the mere presence of these mutations, might be relevant to phenotypic variation in myeloproliferative disorders.
引用
收藏
页码:683 / 687
页数:5
相关论文
共 11 条
  • [1] A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera
    James, C
    Ugo, V
    Le Couédic, JP
    Staerk, J
    Delhommeau, F
    Lacout, C
    Garçon, L
    Raslova, H
    Berger, R
    Bennaceur-Griscelli, A
    Villeval, JL
    Constantinescu, SN
    Casadevall, N
    Vainchenker, W
    [J]. NATURE, 2005, 434 (7037) : 1144 - 1148
  • [2] Mutation studies in CD3+, CD19+ and CD34+ cell fractions in myeloproliferative disorders with homozygous JAK2V617F in granulocytes
    Lasho, TL
    Mesa, R
    Gilliland, DG
    Tefferi, A
    [J]. BRITISH JOURNAL OF HAEMATOLOGY, 2005, 130 (05) : 797 - 799
  • [3] X-inactivation-based clonality analysis and quantitative JAK2V617F assessment reveal a strong association between clonality and JAK2V617F in PV but not ET/MMM, and identifies a subset of JAK2V617F-negative ET and NIMM patients with clonal hematopoiesis
    Levine, Ross L.
    Belisle, Claude
    Wadleigh, Martha
    Zahrieh, David
    Lee, Stephanie
    Chagnon, Pierre
    Gilliland, D. Gary
    Busque, Lambert
    [J]. BLOOD, 2006, 107 (10) : 4139 - 4141
  • [4] The JAK2-V617F mutation is frequently present at diagnosis in patients with essential thrombocythemia and polycythemia vera
    Lippert, Eric
    Boissinot, Marjorie
    Kralovics, Robert
    Girodon, Francois
    Dobo, Irene
    Praloran, Vincent
    Boiret-Dupre, Nathalie
    Skoda, Radek C.
    Hermouet, Sylvie
    [J]. BLOOD, 2006, 108 (06) : 1865 - 1867
  • [5] Validation of two clinically useful assays for evaluation of JAK2 V617F mutation in chronic myeloproliferative disorders
    McClure, R
    Mai, M
    Lasho, T
    [J]. LEUKEMIA, 2006, 20 (01) : 168 - 171
  • [6] PARDANANI A, 2006, BLOOD
  • [7] MPLW515L is anovel somatic activating mutation in myelofibrosis with myeloid metaplasia
    Pikman, Yana
    Lee, Benjamin H.
    Mercher, Thomas
    McDowell, Elizabeth
    Ebert, Benjamin L.
    Gozo, Maricel
    Cuker, Adam
    Wernig, Gerlinde
    Moore, Sandra
    Galinsky, Ilene
    DeAngelo, Daniel J.
    Clark, Jennifer J.
    Lee, Stephanie J.
    Golub, Todd R.
    Wadleigh, Martha
    Gilliland, D. Gary
    Levine, Ross L.
    [J]. PLOS MEDICINE, 2006, 3 (07): : 1140 - 1151
  • [8] Progenitors homozygous for the V617F mutation occur in most patients with polycythemia vera, but not essential thrombocythemia
    Scott, Linda M.
    Scott, Mike A.
    Campbell, Peter J.
    Green, Anthony R.
    [J]. BLOOD, 2006, 108 (07) : 2435 - 2437
  • [9] Tefferi A, 2005, NEW ENGL J MED, V353, P1416
  • [10] VARDIMAN JW, 2001, TUMOURS HAEMATOPOIET, P17