| Orginal Article |
|
|
|
|
| The Genetics of Mixed-phenotype Acute Leukemia |
WANG Qian,CHEN Su-ning( ) |
| The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Suzhou 215006, China |
|
|
|
Abstract Mixed-phenotype acute leukemia (MPAL) is a rare type of acute leukemia, in which the blasts express lineage specific antigens of more than 1 lineage. The incidence of MPAL comprises 2% to 5% of all cases of acute leukemia. Clonal chromosomal abnormalities can be detected in about 59% to 91% of MPAL patients, such as t(9;22)(q34;q11)/BCR-ABL1 and t(v;11q23)/KMT2A-rearrangment, which play a prominent role in the diagnosis and prognosis of these disorders. More recently, molecular approaches have been useful in further characterizing this group of diseases, such as whole genome sequencing, whole exome sequencing and next generation sequencing. ZNF384 fusions are common in B/My MPAL and WT1 mutations are common in T/My MPAL, which provide potential biological insights and may have clinical implications for this disease. This review aims to provide a brief overview of the recent advances in MPAL genetics.
|
|
Received: 19 August 2019
Published: 20 September 2019
|
|
|
|
Corresponding Authors:
Su-ning CHEN
E-mail: chensuning@sina.com
|
|
|
| [1] |
Vardiman J W, Thiele J, Arber D A , et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood, 2009,114(5):937-951.
|
|
|
| [2] |
Arber D A, Orazi A, Hasserjian R , et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood, 2016,127(20):2391-2405.
|
|
|
| [3] |
Matutes E, Pickl W F, Van’t Veer M , et al. Mixed-phenotype acute leukemia: clinical and laboratory features and outcome in 100 patients defined according to the WHO 2008 classification. Blood, 2011,117(11):3163-3171.
doi: 10.1182/blood-2010-10-314682
|
|
|
| [4] |
Porwit A, Bene M C . Acute leukemias of ambiguous origin. Am J Clin Pathol, 2015,144(3):361-376.
|
|
|
| [5] |
Munker R, Brazauskas R, Wang H L , et al. Allogeneic hematopoietic cell transplantation for patients with mixed phenotype acute leukemia. Biol Blood Marrow Transplant, 2016,22(6):1024-1029.
|
|
|
| [6] |
Weinberg O K, Arber D A . Mixed-phenotype acute leukemia: historical overview and a new definition. Leukemia, 2010,24(11):1844-1851.
|
|
|
| [7] |
Yan L, Ping N, Zhu M , et al. Clinical, immunophenotypic, cytogenetic, and molecular genetic features in 117 adult patients with mixed-phenotype acute leukemia defined by WHO-2008 classification. Haematologica, 2012,97(11):1708-1712.
|
|
|
| [8] |
van den Ancker W, Terwijn M, Westers T M , et al. Acute leukemias of ambiguous lineage: diagnostic consequences of the WHO2008 classification. Leukemia, 2010,24(7):1392-1396.
|
|
|
| [9] |
Atfy M ,Al Azizi N M,Elnaggar A M. Incidence of Philadelphia-chromosome in acute myelogenous leukemia and biphenotypic acute leukemia patients: and its role in their outcome. Leuk Res, 2011,35(10):1339-1344.
|
|
|
| [10] |
Bhatia P, Binota J, Varma N , et al. A study on the expression of BCR-ABL transcript in mixed phenotype acute leukemia (MPAL) cases using the reverse transcriptase polymerase reaction assay (RT-PCR) and its correlation with hematological remission status post Initial induction therapy. Mediterr J Hematol Infect Dis, 2012,4(1):e2012024.
|
|
|
| [11] |
Gerr H, Zimmermann M, Schrappe M , et al. Acute leukaemias of ambiguous lineage in children: characterization, prognosis and therapy recommendations. Br J Haematol, 2010,149(1):84-92.
|
|
|
| [12] |
Arana-Trejo R M, Ruiz Sanchez E, Ignacio-Ibarra G , et al. BCR/ABL p210, p190 and p230 fusion genes in 250 Mexican patients with chronic myeloid leukaemia (CML). Clin Lab Haematol, 2002,24(3):145-150.
|
|
|
| [13] |
Moorman A V, Harrison C J, Buck G A , et al. Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL): analysis of cytogenetic data from patients treated on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial. Blood, 2007,109(8):3189-3197.
|
|
|
| [14] |
Kihara R, Nagata Y, Kiyoi H , et al. Comprehensive analysis of genetic alterations and their prognostic impacts in adult acute myeloid leukemia patients. Leukemia, 2014,28(8):1586-1595.
doi: 10.1038/leu.2014.55
|
|
|
| [15] |
Ley T J, Miller C, Ding L , et al. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med, 2013,368(22):2059-2074.
|
|
|
| [16] |
Soupir C P, Vergilio J A, Dal Cin P , et al. Philadelphia chromosome-positive acute myeloid leukemia: a rare aggressive leukemia with clinicopathologic features distinct from chronic myeloid leukemia in myeloid blast crisis. Am J Clin Pathol, 2007,127(4):642-650.
|
|
|
| [17] |
Wolach O, Stone R M . How I treat mixed-phenotype acute leukemia. Blood, 2015,125(16):2477-2485.
|
|
|
| [18] |
Wang Y, Gu M, Mi Y , et al. Clinical characteristics and outcomes of mixed phenotype acute leukemia with Philadelphia chromosome positive and/or bcr-abl positive in adult. Int J Hematol, 2011,94(6):552-555.
doi: 10.1007/s12185-011-0953-1
|
|
|
| [19] |
Al-Seraihy A S, Owaidah T M, Ayas M , et al. Clinical characteristics and outcome of children with biphenotypic acute leukemia. Haematologica, 2009,94(12):1682-1690.
|
|
|
| [20] |
Owaidah T M, Al Beihany A, Iqbal M A , et al. Cytogenetics, molecular and ultrastructural characteristics of biphenotypic acute leukemia identified by the EGIL scoring system. Leukemia, 2006,20(4):620-626.
|
|
|
| [21] |
Shimizu H, Saitoh T, Machida S , et al. Allogeneic hematopoietic stem cell transplantation for adult patients with mixed phenotype acute leukemia: results of a matched-pair analysis. Eur J Haematol, 2015,95(5):455-460.
|
|
|
| [22] |
Zhang Y, Wu D, Sun A , et al. Clinical characteristics, biological profile, and outcome of biphenotypic acute leukemia: a case series. Acta Haematol, 2011,125(4):210-218.
|
|
|
| [23] |
Heesch S, Neumann M, Schwartz S , et al. Acute leukemias of ambiguous lineage in adults: molecular and clinical characterization. Ann Hematol, 2013,92(6):747-758.
doi: 10.1007/s00277-013-1694-4
|
|
|
| [24] |
De Braekeleer E, Meyer C, Douet-Guilbert N , et al. Identification of MLL partner genes in 27 patients with acute leukemia from a single cytogenetic laboratory. Mol Oncol, 2011,5(6):555-563.
doi: 10.1016/j.molonc.2011.08.003
|
|
|
| [25] |
Li Z, Luo R T, Mi S , et al. Consistent deregulation of gene expression between human and murine MLL rearrangement leukemias. Cancer Res, 2009,69(3):1109-1116.
|
|
|
| [26] |
Wang Q F, Wu G, Mi S , et al. MLL fusion proteins preferentially regulate a subset of wild-type MLL target genes in the leukemic genome. Blood, 2011,117(25):6895-6905.
doi: 10.1182/blood-2010-12-324699
|
|
|
| [27] |
Balgobind B V, Raimondi S C, Harbott J , et al. Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study. Blood, 2009,114(12):2489-2496.
|
|
|
| [28] |
Tamai H, Yamaguchi H, Hamaguchi H , et al. Clinical features of adult acute leukemia with 11q23 abnormalities in Japan: a co-operative multicenter study. Int J Hematol, 2008,87(2):195-202.
doi: 10.1007/s12185-008-0034-2
|
|
|
| [29] |
Manola K N . Cytogenetic abnormalities in acute leukaemia of ambiguous lineage: an overview. Br J Haematol, 2013,163(1):24-39.
|
|
|
| [30] |
Rubnitz J E, Onciu M, Pounds S , et al. Acute mixed lineage leukemia in children: the experience of St Jude Children’s Research Hospital. Blood, 2009,113(21):5083-5089.
|
|
|
| [31] |
Xu X Q, Wang J M, Lu S Q , et al. Clinical and biological characteristics of adult biphenotypic acute leukemia in comparison with that of acute myeloid leukemia and acute lymphoblastic leukemia: a case series of a Chinese population. Haematologica, 2009,94(7):919-927.
|
|
|
| [32] |
Lou Z, Zhang C C, Tirado C A , et al. Infantile mixed phenotype acute leukemia (bilineal and biphenotypic) with t(10;11)(p12;q23);MLL-MLLT10. Leuk Res, 2010,34(8):1107-1109.
|
|
|
| [33] |
Daigle S R, Olhava E J, Therkelsen C A , et al. Potent inhibition of DOT1L as treatment of MLL-fusion leukemia. Blood, 2013,122(6):1017-1025.
doi: 10.1182/blood-2013-04-497644
|
|
|
| [34] |
Dawson M A, Prinjha R K, Dittmann A , et al. Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. Nature, 2011,478(7370):529-533.
|
|
|
| [35] |
Takahashi K, Wang F, Morita K , et al. Integrative genomic analysis of adult mixed phenotype acute leukemia delineates lineage associated molecular subtypes. Nat Commun, 2018,9(1):2670.
|
|
|
| [36] |
Alexander T B, Gu Z, Iacobucci I , et al. The genetic basis and cell of origin of mixed phenotype acute leukaemia. Nature, 2018,562(7727):373-379.
|
|
|
| [37] |
Quesada A E, Hu Z, Routbort M J , et al. Mixed phenotype acute leukemia contains heterogeneous genetic mutations by next-generation sequencing. Oncotarget, 2018,9(9):8441-8449.
|
|
|
| [38] |
Eckstein O S, Wang L, Punia J N , et al. Mixed-phenotype acute leukemia (MPAL) exhibits frequent mutations in DNMT3A and activated signaling genes. Exp Hematol, 2016,44(8):740-744.
|
|
|
| [39] |
Noronha E P ,Marques L V C,Andrade F G , et al. T-lymphoid/myeloid mixed phenotype acute leukemia and early T-cell precursor lymphoblastic leukemia similarities with NOTCH1 mutation as a good prognostic factor. Cancer Manag Res, 2019,11:3933-3943.
|
|
|
| [40] |
Hou H A, Kuo Y Y, Liu C Y , et al. DNMT3A mutations in acute myeloid leukemia: stability during disease evolution and clinical implications. Blood, 2012,119(2):559-568.
doi: 10.1182/blood-2011-07-369934
|
|
|
| [41] |
Xiao W, Bharadwaj M, Levine M , et al. PHF6 and DNMT3A mutations are enriched in distinct subgroups of mixed phenotype acute leukemia with T-lineage differentiation. Blood Adv, 2018,2(23):3526-3539.
|
|
|
| [42] |
Alexander T B, Gu Z, Choi J K , et al. Genomic landscape of pediatric mixed phenotype acute leukemia. Blood, 2016,128:454.
|
|
|
| [43] |
Neumann M, Vosberg S, Schlee C , et al. Mutational spectrum of adult T-ALL. Oncotarget, 2015,6(5):2754-2766.
|
|
|
| [44] |
Van Vlierberghe P, Patel J, Abdel-Wahab O , et al. PHF6 mutations in adult acute myeloid leukemia. Leukemia, 2011,25(1):130-134.
doi: 10.1038/leu.2010.247
|
|
|
| [45] |
Wang Q, Qiu H, Jiang H , et al. Mutations of PHF6 are associated with mutations of NOTCH1, JAK1 and rearrangement of SET-NUP214 in T-cell acute lymphoblastic leukemia. Haematologica, 2011,96(12):1808-1814.
doi: 10.3324/haematol.2011.043083
|
|
|
| [46] |
Van Vlierberghe P, Palomero T, Khiabanian H , et al. PHF6 mutations in T-cell acute lymphoblastic leukemia. Nat Genet, 2010,42(4):338-342.
|
|
|
| [47] |
Sood R, Kamikubo Y , Liu P Role of RUNX1 in hematological malignancies. Blood, 2017,129(15):2070-2082.
|
|
|
| [48] |
Ohgami R S, Ma L, Merker J D , et al. Next-generation sequencing of acute myeloid leukemia identifies the significance of TP53, U2AF1, ASXL1, and TET2 mutations. Mod Pathol, 2015,28(5):706-714.
|
|
|
| [49] |
Zhang L, Padron E, Lancet J . The molecular basis and clinical significance of genetic mutations identified in myelodysplastic syndromes. Leuk Res, 2015,39(1):6-17.
|
|
|
|
Viewed |
|
|
|
Full text
|
|
|
|
|
Abstract
|
|
|
|
|
Cited |
|
|
|
|
| |
Shared |
|
|
|
|
| |
Discussed |
|
|
|
|
