Two Cases of Myeloproliferative Neoplasm with a ConcurrentJAK2V617FMutation andBCR/ABLTranslocation without Chronic Myelogenous Leukemia Phenotype Acquisition during Hydroxyurea Treatment

Park, Sang Hyuk; Chi, Hyun‐Sook; Cho, Young‐Uk; Jang, Seongsoo; Park, Chan‐Jeoung; Kim, Dae-Young; Lee, Je‐Hwan; Lee, Kyoo‐Hyung

doi:10.3343/alm.2013.33.3.229

Cited by 17 publications

(7 citation statements)

References 19 publications

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“…However a few cases have been reported in which there was a co-existence of two genetic alterations. In some of these the BCR-ABL1 and JAK2 mutations were found to co-exist [3][4][5][6][7][8][9][10][11].…”

Section: Discussionmentioning

confidence: 99%

“…Previously, it was thought that the JAK2 V617F mutation and BCR-ABL1 translocation were mutually exclusive. However a few rare cases have been reported that are positive for both alterations [4][5][6][7][8][9][10][11][12][13][14][15][16][17]. We report the first case in Central American with the presence of JAK2 V617F mutation, in a patient with the diagnosis of Philadelphia positive chronic myeloid leukemia.…”

Section: Introductionmentioning

confidence: 99%

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Detection of Jak2 V617f Mutation, Secondary to the Presence of Bcr-Abl1 Translocation in a Patient with Chronic Myeloid Leukemia: Report of a Case and Review of the Literature

Tinti¹

2014

Int J Genomic Med

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The myeloproliferative neoplasms are classified in four major diseases: Chronic Myeloid Leukemia, Polycythemia Vera, Primary Myelofibrosis and Essential Thrombocythemia. The JAK2 V617F mutation is found in 95% of Polycythemia Vera, and 50% of Essential Thrombocythemia and Primary Myelofibrosis patients. It was thought that the JAK2 V617F mutation and BCR-ABL1 translocation were mutually exclusive; but now a few cases have been reported with both alterations. We report a rare case with the presence of JAK2 V617F mutation, secondary to a diagnosis of BCR-ABL positive chronic myeloid leukemia. The patient was initially diagnosed as chronic myeloid leukemia and was BCR-ABL1 positive, so he started to receive Imatinib. He responded well to the therapy for three years, but after this time the patient had a hematological relapse still with no detectable copies of BCR-ABL1. For this reason, we thought of the possible development of another genetic alteration. Because the patient had a very high platelet count, we decided to look for the JAK2 V617F mutation, which result was positive. This case is just one of the few that have been reported worldwide that have a coexistence of these two genetic alterations: the BCR-ABL1 transcript and JAK2 V617F mutation in chronic myeloproliferative syndromes. This is the first case in the Central American population, found in our series of a total of 168 patients with Philadelphia positive chronic myeloid leukemia.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Detection of Jak2 V617f Mutation, Secondary to the Presence of Bcr-Abl1 Translocation in a Patient with Chronic Myeloid Leukemia: Report of a Case and Review of the Literature

Tinti¹

2014

Int J Genomic Med

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“…JAK2 including the point mutation is also involved in CML maintenance [18-20]. Thus, JAK2 inhibitors may become a therapeutic target for CML cells.…”

Section: Introductionmentioning

confidence: 99%

“…JAK2 is part of the BCR-ABL signaling network pathway and is activated in CML cells [ 17 ]. JAK2 including the point mutation is also involved in CML maintenance [ 18 - 20 ]. Thus, JAK2 inhibitors may become a therapeutic target for CML cells.…”

Section: Introductionmentioning

confidence: 99%

Combination of the ABL kinase inhibitor imatinib with the Janus kinase 2 inhibitor TG101348 for targeting residual BCR-ABL-positive cells

et al. 2014

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BackgroundThe ABL kinase inhibitor imatinib is highly effective in treating most, but not all, patients with chronic myeloid leukemia (CML). This is because residual CML cells are generally present in the bone marrow microenvironment and are refractory to imatinib. Hematopoietic cytokine receptor signaling is mediated by Janus kinases (JAKs) and their downstream transcription factor, signal transducer and activator of transcription (STAT). TG101348 (SAR302503) is an oral inhibitor of JAK2.MethodsWe investigated the efficacy of imatinib and TG101348 using the break point cluster region-c-Abelson (BCR-ABL)-positive cell line and primary CML samples wherein leukemia cells were protected by a feeder cell line (HS-5).ResultsImatinib treatment resulted in partial inhibition of cell growth in HS-5-conditioned medium. Furthermore, combined treatment with imatinib and TG101348 abrogated the protective effects of HS-5-conditioned medium on K562 cells. Phosphorylation of Crk-L, a BCR-ABL substrate, decreased considerably, while apoptosis increased. In addition, the combined treatment of CD34-positive primary samples resulted in considerably increased cytotoxicity, decreased Crk-L phosphorylation, and increased apoptosis. We also investigated TG101348 activity against feeder cells and observed that STAT5 phosphorylation, granulocyte macrophage colony-stimulating factor, and interleukin 6 levels decreased, indicating reduced cytokine production in HS-5 cells treated with TG101348.ConclusionsThese results showed that JAK inhibitors may enhance the cytotoxic effect of imatinib against residual CML cells and that a combined approach may be a powerful strategy against the stroma-associated drug resistance of Philadelphia chromosome-positive cells.

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“…Based on the occurrence of chromosomal abnormality t(9; 22) that results in the formation of BCR/ABL oncoprotein, MPNs are stratified as either Philadelphia (Ph)-chromosome positive chronic myeloid leukemia (CML) or Ph-chromosome negative MPNs, such as primary myelofibrosis, polycythemia vera (PV), and essential thrombocythemia [2]. Until a decade back, the presence of BCR/ABL and JAK2 V617F mutation (or the other two Ph chromosome-negative MPN driver mutations, in CALR or MPLW515 ) were considered mutually exclusive.…”

Section: Introductionmentioning

confidence: 99%

Unique Case of Myeloproliferative Neoplasm with Two Rare Clonal Abnormalities: Rare JAK2 Exon 12 Mutation and Rare e14a3 (b3a3) BCR/ABL Fusion Transcript

et al. 2018

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Myeloproliferative neoplasms (MPNs) are clonal disorders divided into Philadelphia (Ph) chromosome-positive chronic myeloid leukemia (CML) or Ph chromosome-negative MPNs. Co-occurrence of these disease entities is very rare and typically involves presence of common p190 or p210 BCR/ABL fusion transcript (responsible for CML) along with JAK2^V617F mutation (most common driver mutation in Ph-negative MPNs). Because of the rarity of such cases, it is not clear if the outcomes are any different in these patients. In this article, we report a unique patient with polycythemia vera driven by a rare complex in-frame deletion-insertion mutation in JAK2 exon 12, and CML driven by uncommon p210 e14a3 (b3a3) BCR/ABL fusion transcript. We describe clinical and laboratory features, bone marrow pathology, treatment, and overall outcome.

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Two Cases of Myeloproliferative Neoplasm with a ConcurrentJAK2^V617FMutation andBCR/ABLTranslocation without Chronic Myelogenous Leukemia Phenotype Acquisition during Hydroxyurea Treatment

Cited by 17 publications

References 19 publications

Detection of Jak2 V617f Mutation, Secondary to the Presence of Bcr-Abl1 Translocation in a Patient with Chronic Myeloid Leukemia: Report of a Case and Review of the Literature

Detection of Jak2 V617f Mutation, Secondary to the Presence of Bcr-Abl1 Translocation in a Patient with Chronic Myeloid Leukemia: Report of a Case and Review of the Literature

Combination of the ABL kinase inhibitor imatinib with the Janus kinase 2 inhibitor TG101348 for targeting residual BCR-ABL-positive cells

Unique Case of Myeloproliferative Neoplasm with Two Rare Clonal Abnormalities: Rare <b><i>JAK2</i></b> Exon 12<b><i></i></b> Mutation and Rare e14a3 (b3a3) BCR/ABL Fusion Transcript

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