Myelofibrosis evolving during imatinib treatment of a chronic myeloproliferative disease with coexisting BCR-ABL translocation and JAK2V617F mutation

Hussein, Kais; Böck, O.; A, Seegers; Flaßhove, Michael; Henneke, Felicitas; Buesche, Guntram; Kreipe, Hans

doi:10.1182/blood-2006-12-061135

Cited by 97 publications

(84 citation statements)

References 7 publications

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“…24 Clonal heterogeneity has also been implicated in rare cases of myeloproliferative neoplasms with combined BCR-ABL1 and JAK2 mutation-positivity. 25,26 In these cases, a BCR-ABL1-negative clone carrying JAK2 mutation appears during the course of imatinib treatment. In addition, clonal heterogeneity has been demonstrated in cases of myeloproliferative neoplasms with del(20q) 27 and myelodysplastic syndromes with isolated 5q deletion associated with JAK2 mutation.…”

Section: Discussionmentioning

confidence: 99%

Development of monocytosis in patients with primary myelofibrosis indicates an accelerated phase of the disease

et al. 2013

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Primary myelofibrosis is a type of chronic myeloproliferative neoplasm characterized by progressive bone marrow failure with worsening cytopenia and in a subset of patients, progression to acute leukemia. Published data in patients with myelodysplastic syndromes have shown that the development of monocytosis in the course of myelodysplastic syndromes is associated with a poor prognosis. A similar occurrence has been only sporadically reported in patients with primary myelofibrosis. Over a period of four years we identified 10 out of 237 cases of primary myelofibrosis who developed persistent absolute monocytosis (41 Â 10 9 /l) during the course of disease (5 men and 5 women; median age/range: 68 years/52-82). Monocytosis developed at a median interval of 42 months from diagnosis (range: 1-180) and persisted for a median period of 23 months (range: 2-57). Five patients died after developing monocytosis (range: 20-188 months) and two experienced worsening disease and became transfusion dependent. Monocytosis was associated with increased white blood cells, decreased hemoglobin, decreased platelet count, and the presence of circulating blasts. In three cases, bone marrow biopsies after the onset of monocytosis showed marked myelomonocytic proliferation with morphological shifting from a typical primary myelofibrosis marrow appearance to aspects compatible with an overt 'secondary' chronic myelomonocytic leukemia. Before the development of monocytosis, 5 of 10 patients carried the JAK2V617F mutation; five patients showed karyotypic alterations. No change in JAK2 mutational status or cytogenetic evolution were associated with the development of monocytosis. Four of nine patients analyzed showed KRAS mutation in codon 12 or 13 with low allele burden. This is the first study correlating monocytosis developing in primary myelofibrosis patients with bone marrow morphology, laboratory data, molecular analysis and clinical follow-up. Development of monocytosis in patients with established primary myelofibrosis is associated with rapid disease progression and these patients should be considered as a high-risk group associated with short survival.

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Section: Discussionmentioning

confidence: 99%

Development of monocytosis in patients with primary myelofibrosis indicates an accelerated phase of the disease

et al. 2013

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“…1 A subgroup of Ph þ -CML mimics ET or PMF by presenting with marked thrombocytosis or myelofibrosis (MF), but only single cases with concomitant Ph þ -CML and Ph À -CMPD were reported so far. [2][3][4][5] Recently, our group Inami et al, Krämer et al, and Bornhäuser et al [2][3][4][5] simultaneously reported on four well-documented cases with concurrent JAK2 V617F and BCR-ABL translocation ( Table 1). The tyrosine kinase abnormalities appeared to affect independent subclones because imatinib mesylate (IM) treatment induced Ph þ -CML remission whereas the JAK2 V617F clone either persisted or became clinically manifest as PMF [2][3][4] or PV.…”

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confidence: 99%

“…5 In our previously reported case, a minor JAK2 V617F clone expanded after major response of Ph þ -CML to IM. 2 In search for parallel cases, we discovered a total of four CMPD cases of concurrent BCR-ABL and JAK2 V617F mutation in the Hannover bone marrow registry (Table 1). In one of these Ph þ -CML cases similar to the previously published cases, 2-5 the concurrent JAK2 V617F clone became clinically manifest subsequently to IM-induced suppression of the BCR-ABL clone.…”

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confidence: 99%

Chronic myeloproliferative diseases with concurrent BCR–ABL junction and JAK2V617F mutation

et al. 2007

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Concerning response to treatment and overall prognosis, all patients experienced a complete response to induction therapy with rapid decrease in leukocytosis and resolution of extramedullary involvement under corticosteroid therapy. MRD, when applicable, was found negative at the end of induction, underlying high sensitivity to chemotherapy. This high chemosensitivity contrasted with the high incidence of relapse (occurring in three of our cases) and poor overall prognosis. This finding underlines the importance of quick identification of this rearrangement to propose treatment adaptation to high-risk groups, including allogeneic marrow transplantation consideration before facing potentially chemoresistant relapse.In summary, we describe here five cases of mature 'sIg þ ' B-ALL with non FAB-L3 morphology displaying 11q23-MLL rearrangement, and especially t(9;11), occurring in young children with a poor prognosis and requiring treatment intensification.

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“…Subsequently, 25 ng of DNA were used for PCR amplification of JAK2 and MPL fragments (GenBank AL161450; U68161) and pyrosequencing® in a PSQ 96MA instrument (Biotage, Uppsala, Sweden) was performed as described [17,20]. JAK2 V617F cell line HEL, MPL W515L PMF patient sample and JAK2 wild-type / MPL wild-type cell line HL-60 were used as controls.…”

Section: Bone Marrow Study Group and Ethical Backgroundmentioning

confidence: 99%

Megakaryocytic expression of miRNA 10a, 17-5p, 20a and 126 in Philadelphia chromosome-negative myeloproliferative neoplasm

et al. 2008

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International audienceMicro RNA (miRNA) are small non-coding RNA molecules which have a post-transcriptional inhibitory regulation function, e.g. in megakaryopoiesis. A characteristic of Philadelphia chromosome-negative myeloproliferative neoplasm (Ph MPN) is the abundance of morphologically aberrant megakaryocytes. Based on previously published in vitro megakaryocytic differentiation assay data, we selected miRNA 10a, 17-5p, 20a and 126 and potential target proteins (HOXA1, RUNX1) for analysis of laser-microdissected bone marrow megakaryocytes from Ph MPN and controls ( = 66). Furthermore, we tested a potential influence of cytoreductive treatment on miRNA expression in bone marrow cells during the course of Ph MPN ( = 18). In summary, miRNA 17-5p, 20a and 126 are constitutively expressed in Ph MPN megakaryopoiesis while low or absent miRNA 10a appeared to correlate with strong megakaryocytic HOXA1 protein expression. No association to thrombocytosis, JAK2 mutations or cytoreductive treatment (bone marrow cells) were observed

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Myelofibrosis evolving during imatinib treatment of a chronic myeloproliferative disease with coexisting BCR-ABL translocation and JAK2V617F mutation

Cited by 97 publications

References 7 publications

Development of monocytosis in patients with primary myelofibrosis indicates an accelerated phase of the disease

Development of monocytosis in patients with primary myelofibrosis indicates an accelerated phase of the disease

Chronic myeloproliferative diseases with concurrent BCR–ABL junction and JAK2V617F mutation

Megakaryocytic expression of miRNA 10a, 17-5p, 20a and 126 in Philadelphia chromosome-negative myeloproliferative neoplasm

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