An Exercise in Extrapolation: Clinical Management of Atypical CML, MDS/MPN-Unclassifiable, and MDS/MPN-RS-T.
According to the recently published 2016 World Health Organization (WHO) classification of myeloid malignancies, myelodysplastic/myeloproliferative neoplasms (MDS/MPN) include atypical chronic myeloid leukemia (aCML), MDS/MPN-unclassifiable (MDS/MPN-U), chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), and MDS/MPN ring sideroblasts with thrombocytosis (MDS/MPN-RS-T). MDS/MPN-RS-T was previously a provisional category known as refractory anemia with ring sideroblasts with thrombocytosis (RARS-T) which has now attained a distinct designation in the 2016 WHO classification. In this review, we focus on biology and management of aCML, MDS/MPN-U, and MDS/MPN-RS-T. There is considerable overlap between these entities which we attempt to further elucidate in this review. We also discuss recent advances in the field of molecular landscape that further defines and characterizes this heterogeneous group of disorders. The paucity of clinical trials available secondary to unclear pathogenesis and rarity of these diseases makes the management of these entities clinically challenging. This review summarizes some of the current knowledge of the molecular pathogenesis and suggested treatment guidelines based on the available data.
H. Lee Moffitt Cancer Center and Research Institute, Malignant Hematology, Tampa, FL, USA.
Chetasi
C
Talati
H. Lee Moffitt Cancer Center and Research Institute, Malignant Hematology, Tampa, FL, USA. eric.padron@moffitt.org.
Eric
E
Padron
D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D003582:Cytogenetics; D056915:DNA Copy Number Variations; D019337:Hematologic Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D019190:Iron Overload / Q000150:complications; D054438:Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D054437:Myelodysplastic-Myeloproliferative Diseases / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D016184:Receptors, Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D013922:Thrombocytosis / Q000150:complications
C517047:CSF3R protein, human; D002352:Carrier Proteins; D009687:Nuclear Proteins; D047428:Protein Kinase Inhibitors; D016184:Receptors, Colony-Stimulating Factor; C425066:SETBP1 protein, human
Chronic myelomonocytic leukemia; Juvenile myelomonocytic leukemia; Myelodysplastic syndrome; Myeloproliferative neoplasms
N Engl J Med. 1995 Apr 27;332(17):1132-6
7700286
N Engl J Med. 2013 Dec 19;369(25):2379-90
24325356
Blood. 2013 Jan 10;121(2):260-9
23160465
Cureus. 2015 Dec 17;7(12):e414
26870618
Clin Cancer Res. 2016 Feb 1;22(3):757-64
26475333
Leukemia. 2014 Jun;28(6):1374-6
24476766
Rev Bras Hematol Hemoter. 2013;35(3):218-9
23904814
Leuk Res. 2012 Sep;36(9):1147-51
22578777
Onco Targets Ther. 2016 Apr 15;9:2273-86
27143923
Pol J Pathol. 2010;61(2):105-9
20924996
Clin Lymphoma Myeloma Leuk. 2014 Sep;14 Suppl:S36-41
25486953
Blood. 2014 Apr 24;123(17):2645-51
24627528
Blood. 2015 Mar 19;125(12):1857-65
25624319
Case Rep Hematol. 2013;2013:718480
23653870
Clin Lymphoma Myeloma Leuk. 2015 Jun;15 Suppl:S50-5
26297278
J Clin Oncol. 2001 Jun 1;19(11):2915-26
11387365
Nihon Rinsho. 2001 Dec;59(12):2401-6
11766346
Blood. 2010 Jul 15;116(2):180-2
20194893
Ann Oncol. 2000 Apr;11(4):441-4
10847463
Blood. 2016 May 19;127(20):2391-405
27069254
Int J Hematol. 2002 Nov;76(4):344-8
12463598
Haematologica. 2015 Apr;100(4):e125-7
25527566
Haematologica. 2012 Jul;97(7):1036-41
22532522
Blood. 1991 Jul 1;78(1):205-11
2070054
Rinsho Ketsueki. 2016 Feb;57(2):147-55
26935632
Ann Hematol. 2009 Dec;88(12):1207-13
19415278
Blood. 2013 Sep 5;122(10):1707-11
23896413
Nat Genet. 2010 Jun;42(6):483-5
20436468
Leukemia. 2013 Sep;27(9):1826-31
23594705
Leuk Lymphoma. 2013 Oct;54(10):2322-4
23432689
Nat Genet. 2013 Jan;45(1):18-24
23222956
Rinsho Ketsueki. 2013 Jun;54(6):538-44
23823092
Blood. 2008 Feb 1;111(3):1748
18223181
Blood. 2012 May 17;119(20):4614-8
22422826
RNA. 2016 Mar;22(3):350-9
26742993
Cancer. 2003 Jun 1;97(11):2760-6
12767088
Blood. 2015 Jan 15;125(3):499-503
25343957
N Engl J Med. 2013 May 9;368(19):1781-90
23656643
Bone Marrow Transplant. 2004 Dec;34(12):1047-50
15516946
Haematologica. 2006 Nov;91(11):1566-8
17043019
Int J Lab Hematol. 2016 May;38 Suppl 1:12-9
27161873
N Engl J Med. 2011 Oct 13;365(15):1384-95
21995386
Leukemia. 2013 Sep;27(9):1852-60
23628959
Rinsho Ketsueki. 2016 Feb;57(2):137-46
26935631
Int J Hematol. 2015 Mar;101(3):229-42
25212680
Leukemia. 2014 Apr;28(4):958-61
24492324