Chronic myeloid leukemia: mechanisms of blastic transformation

Perrotti, Danilo; Goldman, John M.; Skórski, Tomasz

doi:10.1172/jci41246

Cited by 359 publications

(386 citation statements)

References 140 publications

(186 reference statements)

Supporting

Mentioning

367

Contrasting

Unclassified

Order By: Relevance

“…In the CP of CML, BCR‐ABL1 is a major driver of disease evolution, cell survival and proliferation. By contrast, in AP and BP, additional factors and pro‐oncogenic molecules play a critical role in disease progression and drug resistance 4, 5, 6, 9, 10, 11. A key laboratory feature of patients with advanced CML is marked and sometimes even excessive basophilia 12, 13, 14.…”

Section: Introductionmentioning

confidence: 99%

The underestimated role of basophils in Ph⁺ chronic myeloid leukaemia

Valent

Horny

Arock

2018

Eur J Clin Investigation

View full text Add to dashboard Cite

Chronic myeloid leukaemia (CML) is a hematopoietic neoplasm defined by the chromosome translocation t(9;22) and the related oncogene, BCR‐ABL1. In most patients, leukaemic cells can be kept under control using BCR‐ABL1‐targeting drugs. However, many patients relapse which remains a clinical challenge. In particular, patients with advanced (accelerated or blast phase) CML have a poor prognosis. So far, little is known about molecular and cellular interactions and features that contribute to disease progression and drug resistance in CML. One key prognostic factor at diagnosis is marked basophilia. However, although basophils are well‐known multifunctional effector cells, their impact in CML remains uncertain. In this article, we discuss the potential role of basophils as active contributors to disease evolution and progression in CML. In particular, basophils serve as a unique source of inflammatory, angiogenic and fibrogenic molecules, such as vascular endothelial growth factor or hepatocyte growth factor. In addition, basophils provide vasoactive substances, like histamine as well as the cytokine‐degrading enzyme dipeptidyl‐peptidase IV which may promote stem cell mobilization and the extramedullary spread of stem and progenitor cells. Finally, basophils may produce autocrine growth factors for myeloid cells. Understanding the role of basophils in CML evolution and progression may support the development of more effective treatment concepts.

show abstract

Section: Introductionmentioning

confidence: 99%

The underestimated role of basophils in Ph⁺ chronic myeloid leukaemia

Valent

Horny

Arock

2018

Eur J Clin Investigation

View full text Add to dashboard Cite

show abstract

“…1,2 In approximately 70% of cases the blast lineage is myeloid, whereas in 20-30% of cases the blasts are lymphoid. 3 It has been suggested that the progression of CML to BC-CML is a two-step process.…”

mentioning

confidence: 99%

“…3 After translocating from the cytoplasm to the nucleus, it may cause genetic instability by unfaithful DNA repair, which contributes to structural chromosomal aberrations or mutations of transcription factors in hematopoietic stem cells. 1,5 Ultimately, the accumulation of chromosomal and molecular alterations is responsible for the transformation to BC-CML. Of note, no significant differences were observed with respect to associations between BCR-ABL mutations and additional molecular mutations or chromosomal alterations in addition to t(9;22).…”

mentioning

confidence: 99%

“…As only 4/13 of cases with mutated RUNX1 were concomitantly mutated in BCR-ABL (Figure 1), we suggest that abnormalities in RUNX1 have an independent role in tyrosine kinase inhibitor resistance and may contribute to treatment failure. 1,8 Figure 1 Frequencies and distribution of mutations. Frequencies are given for molecular mutations in RUNX1, ASXL1, IKZF1, WT1, TET2, IDH1, NRAS, KRAS, CBL and TP53.…”

mentioning

confidence: 99%

“…Marked differences in terms of outcome of AML patients have been confirmed to be related to the presence of specific genetic aberrations. 1 A subset of high-risk AML patients is characterized by rearrangements, involving the mixed-lineage leukemia gene (MLL) located on chromosome 11q23. More than 40 different translocation fusion partners of MLL have been identified in AML at diagnosis; however, five partner genes account for over 90% of MLL-translocated pediatric AML (AF9, AF10, AF6, ENL and ELL).…”

mentioning

confidence: 99%

See 2 more Smart Citations

A deep-sequencing study of chronic myeloid leukemia patients in blast crisis (BC-CML) detects mutations in 76.9% of cases

et al. 2011

View full text Add to dashboard Cite

nuclear staining (480% of neoplastic cells) for MATK is seen in all 22 type II EATLs, including unusual cases that are CD8 À but are otherwise indistinguishable from ordinary type II EATL. More variable amount of nuclear staining (ranging from 20 to 480%) for MATK is seen in 58 cases of NK/T-cell lymphoma (NKTL).In conclusion, we have identified a novel marker of type II EATL that shows a distinctive nuclear staining pattern in the vast majority of neoplastic cells. This marker is a useful additional tool in the diagnostic workup of this rare neoplasm, particularly in cases that lack the characteristic CD8 expression (Figure 1).

show abstract