Single cell analysis exposes intratumor heterogeneity and suggests that FLT3-ITD is a late event in leukemogenesis

Experimental Hematology

Volumn 42, Issue 6, 2014, Pages 457-463

  Shouval, Roni ^a   Shlush, Liran I ^b   Yehudai Resheff, Shlomit ^c   Ali, Shahnaz ^a   Pery, Neta ^a   Shapiro, Ehud ^b   Tzukerman, Maty ^a   Rowe, Jacob M ^a,c,d   Zuckerman, Tsila ^a,c  

^a TECHNION ISRAEL INSTITUTE OF TECHNOLOGY   (Israel)

^b WEIZMANN INSTITUTE OF SCIENCE   (Israel)

^c Department of Hematology Bone Marrow Transplantation Rambam Health Care Campus ^*  (Israel)

^d SHAARE ZEDEK MEDICAL CENTER   (Israel)

Author keywords

[No Author keywords available]

Indexed keywords

CD135 ANTIGEN;

ACUTE GRANULOCYTIC LEUKEMIA; ACUTE LYMPHOBLASTIC LEUKEMIA; ADULT; AGED; ALLELE; ARTICLE; CLINICAL ARTICLE; CLONE; CONTROLLED STUDY; DNA DETERMINATION; FLT3 GENE; GENE DUPLICATION; GENE FREQUENCY; GENE LOSS; GENE MUTATION; GENETIC HETEROGENEITY; GENETIC VARIABILITY; HETEROZYGOSITY; HUMAN; HUMAN CELL; INTERMETHOD COMPARISON; INTERNAL TANDEM DUPLICATION; LEUKEMIA CELL; LEUKEMIA RELAPSE; LEUKEMOGENESIS; MONONUCLEAR CELL; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; SINGLE CELL ANALYSIS;

ADULT; AGED; ALLELES; CARCINOGENESIS; FMS-LIKE TYROSINE KINASE 3; GENE DUPLICATION; HUMANS; LEUKEMIA; LEUKOCYTES; MIDDLE AGED; RECURRENCE; SINGLE-CELL ANALYSIS; T-LYMPHOCYTES; TIME FACTORS;

EID: 84902685635     PISSN: 0301472X     EISSN: 18732399     Source Type: Journal    
DOI: 10.1016/j.exphem.2014.01.010     Document Type: Article

References (33)

1. Kiyoi H., Yanada M., Ozekia K. Clinical significance of FLT3 in leukemia. Int J Hematol 2005, 82:85-92.
2. Meshinchi S., Appelbaum F.R. Structural and functional alterations of FLT3 in acute myeloid leukemia. Clin Cancer Res 2009, 15:4263-4269.
3. Thiede C., Steudel C., Mohr B., et al. Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis. Blood 2002, 99:4326-4335.
4. Smith C.C., Wang Q., Chin C.S., et al. Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia. Nature 2012, 485:260-263.
5. Chang P., Kang M., Xiao A., et al. FLT3 mutation incidence and timing of origin in a population case series of pediatric leukemia. BMC Cancer 2010, 10:513.
6. Xu F., Taki T., Yang H.W., et al. Tandem duplication of the FLT3 gene is found in acute lymphoblastic leukaemia as well as acute myeloid leukaemia but not in myelodysplastic syndrome or juvenile chronic myelogenous leukaemia in children. Br J Haematol 1999, 105:155-162.
7. Shlush L.I., Chapal-Ilani N., Adar R., et al. Cell lineage analysis of acute leukemia relapse uncovers the role of replication-rate heterogeneity and microsatellite instability. Blood 2012, 120:603-612.
8. Kottaridis P.D., Gale R.E., Langabeer S.E., et al. Studies of FLT3 mutations in paired presentation and relapse samples from patients with acute myeloid leukemia: implications for the role of FLT3 mutations in leukemogenesis, minimal residual disease detection, and possible therapy with FLT3 inhibitors. Blood 2002, 100:2393-2398.
9. Testa U., Pelosi E. The impact of FLT3 mutations on the development of acute myeloid leukemias. Leuk Res Treatment 2013, 2013:275760.
10. Kiyoi H., Naoe T. FLT3 mutations in acute myeloid leukemia. Methods Mol Med 2006, 125:189-197.
11. Altschuler S.J., Wu L.F. Cellular heterogeneity: do differences make a difference?. Cell 2010, 141:559-563.
12. Ding L., Ley T.J., Larson D.E., et al. Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing. Nature 2012, 481:506-510.
13. Welch J.S., Ley T.J., Link D.C., et al. The origin and evolution of mutations in acute myeloid leukemia. Cell 2012, 150:264-278.
14. Walter M.J., Shen D., Ding L., et al. Clonal architecture of secondary acute myeloid leukemia. N Engl J Med 2012, 366:1090-1098.
15. Meshinchi S., Alonzo T.A., Stirewalt D.L., et al. Clinical implications of FLT3 mutations in pediatric AML. Blood 2006, 108:3654-3661.
16. Abu-Duhier F.M., Goodeve A.C., Wilson G.A., et al. FLT3 internal tandem duplication mutations in adult acute myeloid leukaemia define a high-risk group. Br J Haematol 2000, 111:190-195.
17. Smith C.A., Williams G.T., Kingston R., et al. Antibodies to CD3/T-cell receptor complex induce death by apoptosis in immature T cells in thymic cultures. Nature 1989, 337:181-184.
18. Hope K.J., Jin L., Dick J.E. Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity. Nat Immunol 2004, 5:738-743.
19. Greaves M. Darwin and evolutionary tales in leukemia. The Ham-Wasserman Lecture. Hematology Am Soc Hematol Educ Program 2009, 3-12.
20. Gerlinger M., Rowan A.J., Horswell S., et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 2012, 366:883-892.
21. Parkin B., Ouillette P., Li Y., et al. Clonal evolution and devolution after chemotherapy in adult acute myelogenous leukemia. Blood 2013, 121:369-377.
22. Pratcorona M., Brunet S., Nomdedeu J., et al. Favorable outcome of patients with acute myeloid leukemia harboring a low-allelic burden FLT3-ITD mutation and concomitant NPM1 mutation: relevance to post-remission therapy. Blood 2013, 121:2734-2738.
23. Walter M.J., Graubert T.A., Dipersio J.F., et al. Next-generation sequencing of cancer genomes: back to the future. Per Med 2009, 6:653.
24. Klein C.A., Schmidt-Kittler O., Schardt J.A., et al. Comparative genomic hybridization, loss of heterozygosity, and DNA sequence analysis of single cells. Proc Natl Acad Sci USA 1999, 96:4494-4499.
25. Ley T.J., Mardis E.R., Ding L., et al. DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome. Nature 2008, 456:66-72.
26. Man C.H., Fung T.K., Ho C., et al. Sorafenib treatment of FLT3-ITD(+) acute myeloid leukemia: favorable initial outcome and mechanisms of subsequent nonresponsiveness associated with the emergence of a D835 mutation. Blood 2012, 119:5133-5143.
27. Cloos J., Goemans B.F., Hess C.J., et al. Stability and prognostic influence of FLT3 mutations in paired initial and relapsed AML samples. Leukemia 2006, 20:1217-1220.
28. Raghavan M., Smith L.L., Lillington D.M., et al. Segmental uniparental disomy is a commonly acquired genetic event in relapsed acute myeloid leukemia. Blood 2008, 112:814-821.
29. Tuna M., Knuutila S., Mills G.B. Uniparental disomy in cancer. Trends Mol Med 2009, 15:120-128.
30. Gupta M., Raghavan M., Gale R.E., et al. Novel regions of acquired uniparental disomy discovered in acute myeloid leukemia. Genes Chromosomes Cancer 2008, 47:729-739.
31. Kharazi S., Mead A.J., Mansour A., et al. Impact of gene dosage, loss of wild-type allele, and FLT3 ligand on Flt3-ITD-induced myeloproliferation. Blood 2011, 118:3613-3621.
32. Li L., Piloto O., Nguyen H.B., et al. Knock-in of an internal tandem duplication mutation into murine FLT3 confers myeloproliferative disease in a mouse model. Blood 2008, 111:3849-3858.
33. Stone R.M., Fischer T., Paquette R., et al. Phase IB study of the FLT3 kinase inhibitor midostaurin with chemotherapy in younger newly diagnosed adult patients with acute myeloid leukemia. Leukemia 2012, 26:2061-2068.