scholarly journals Myeloproliferative Neoplasm or Reactive Process? A Rare Case of Acute Myeloid Leukemia and Transient Posttreatment Megakaryocytic Hyperplasia with JAK-2 Mutation

2016 ◽  
Vol 2016 ◽  
pp. 1-5
Author(s):  
Steven Wang ◽  
Jie Yan ◽  
Guangde Zhou ◽  
Rebecca Heintzelman ◽  
J. Steve Hou
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Rare Case ◽  
Myeloproliferative Neoplasms ◽  
Jak2 V617f ◽  
Jak2 V617f Mutation ◽  
Cell Transplant ◽  
Jak2 Mutation ◽  
V617f Mutation ◽  
Acute Myeloid

Myeloproliferative neoplasms (MPNs) are hematopoietic malignancies characterized by unchecked proliferation of differentiated myeloid cells. The most common BCR-ABL1-negative MPNs are polycythemia vera, essential thrombocythemia, and primary myelofibrosis. The discovery of JAK2 V617F mutation has improved our understanding of the molecular basis of MPN. The high frequency of JAK2 mutation in MPN makes JAK2 mutation testing an essential diagnostic tool and potential therapeutic target for MPN. Here, we present a rare case of a 34-year-old patient who was initially diagnosed with acute myeloid leukemia (AML) with mutated NPM1. After chemotherapy treatment followed by granulocyte colony stimulating factor administration, the patient achieved complete remission of AML. However, the bone marrow showed hypercellularity with granulocytic hyperplasia, markedly increased atypical megakaryocytes (50.2/HPF) with focal clustering, and reticulin fibrosis (3/4). JAK2 V617F mutation was also detected. Considering the possibility of AML transformed from a previous undiagnosed MPN, patient underwent peripheral blood allogenic stem cell transplant. This case illustrates the diagnostic challenges of firmly establishing a diagnosis between similar, but distinct, disease entities and an accurate clinicopathological differentiation is crucial.

A JAK2-V617F Activating Mutation in Addition to C-KIT and FLT3 Mutations Is Associated with Clinical Outcome in Patients with t(8;21)(q22;q22;) Acute Myeloid Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3492-3492
Author(s):  
Tomoko Nanri ◽  
Eisaku Iwanaga ◽  
Naofumi Matsuno ◽  
Toshiro Kawakita ◽  
Hitoshi Suzushima ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Clinical Outcome ◽  
Tyrosine Kinase ◽  
Myeloid Leukemia ◽  
Jak2 V617f ◽  
Jak2 Mutation ◽  
Flt3 Mutations ◽  
V617f Mutation ◽  
Genetic Events ◽  
Acute Myeloid

Abstract AML1-MTG8 generated by t(8;21)(q22:q22) contributes to leukemic transformation but additional events are required for full leukemogenesis. Mutations in the receptor tyrosine kinase (RTK) including C-KIT and FLT3 genes appear to be the genetic events that cause acute myeloid leukemia (AML) harboring t(8;21) and are associated with unfavorable prognosis (Nanri et al. Leukemia19:1361;2005). On the other hand, the activating V617F mutation in the JAK2 cytoplasmic tyrosine kinase has been detected in a significant proportion of patients with myeloproliferative disorders. Although the same mutation has been identified in a small number of AML patients, it is likely that a relatively high incidence of JAK2-V617F mutation has been seen in t(8;21) AML patients. However, whether they are associated with other biological parameters and whether they influence clinical prognosis in patients with t(8;21) AML have not been determined. To clarify the biological and prognostic impact of the JAK2 mutation, we examined the clinical and prognostic relevance of the mutation. Of 45 patients with t(8;21) AML, mutations in the C-KIT and internal tandem duplications (ITD) in the FLT3 were observed in 18 (40%) and 3 (6.7%), respectively. We detected the JAK2-V617F mutation in 3 patients with t(8;21) AML (6.7%), which was consistent with previous studies. Although the occurrence of C-KIT and FLT3 mutations was mutually exclusive, one patient harboring JAK2 mutation also had a C-KIT second tyrosine kinase mutation and another one patient had a K-RAS mutation. Collectively, a total of 23 (51%) patients showed mutations in the RTK pathway. One patient carrying both C-KIT and JAK2 mutations did not respond to multiple induction chemotherapies. Another patient with the JAK2 and K-RAS mutations achieved a complete remission (CR) but later relapsed. Remaining one patient received allogeneic stem cell transplantation during first CR and continued CR. As we were limited to study a small number of mutated cases for a comparison of clinical and genetic features, we examined the clinical significance of C-KIT, FLT3 and JAK2 mutations as a collective group. A cumulative incidence of relapse (CIR) in 21 patients with RTK mutations was 77%, whereas CIR in 19 patients lacking mutations was 26% (P=0.0083). The 6-year relapse-free survival in patients with mutations was 20% compared to 54% in those without mutations (P=0.0595). These results suggest that the mutations in the JAK2, C-KIT and FLT3 could be an additional genetic events leading to the development of AML and are associated with the clinical outcome in patients with t(8;21) AML.

scholarly journals Essential thrombocythemia during treatment of acute myeloid leukemia with JAK2 V617F mutation

Medicine ◽  
2018 ◽  
Vol 97 (27) ◽  
pp. e11331 ◽  
Author(s):  
Wenwen Ding ◽  
Danni Li ◽  
Chao Zhuang ◽  
Pingping Wei ◽  
Wenfeng Mou ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Essential Thrombocythemia ◽  
Myeloid Leukemia ◽  
Jak2 V617f ◽  
Jak2 V617f Mutation ◽  
V617f Mutation ◽  
Acute Myeloid

scholarly journals Acute myeloid leukemia with MYC rearrangement and JAK2 V617F mutation

2015 ◽  
Vol 208 (11) ◽  
pp. 571-574 ◽  
Author(s):  
Maro Ohanian ◽  
Carlos Bueso-Ramos ◽  
Chi Young Ok ◽  
Pei Lin ◽  
Keyur Patel ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Jak2 V617f ◽  
Jak2 V617f Mutation ◽  
V617f Mutation ◽  
Acute Myeloid

Clinical Characteristics of JAK2 V617F Mutation Positive Acute Myeloid Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4508-4508
Author(s):  
Sarolta Nahajevszky ◽  
Hajnalka Andrikovics ◽  
Zoltan Matrai ◽  
Nora Lovas ◽  
Sandor Lueff ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Clinical Characteristics ◽  
De Novo ◽  
Age Of Onset ◽  
Jak2 V617f ◽  
Blastic Transformation ◽  
V617f Mutation ◽  
Acute Myeloid ◽  
Time Point

Abstract Chronic myeloproliferative diseases (CMPD) are clonal disorders of pluripotent hematopoietic stem cells. Acquired JAK2 V617F point mutation has recently been identified as disease causing activating genetic abnormality in classic BCR-ABL negative CMPD (80% of polycythemia vera, 35% of essential thrombocythemia and 50% of chronic idiopathic myelofibrosis cases). JAK2 V617F is rare in other myeloid stem cell disorders like acute myeloid leukemia, chronic myelomonocyter leukemia or myelodysplasia with reported frequency of 3–8%. Between January 2001 and December 2005 155 consecutive adult patients [87 females and 68 males, median age of onset was 49±14 (range 18–83) years] were diagnosed with AML in our institute. Peripheral blood or bone marrow samples drawn at the time point of diagnosis were analyzed for the presence of JAK2 V617F by allele-specific PCR. JAK2 V617F mutation was present in 5 patients (3 males and 2 females; 3.2%). 3 of the 5 patients had prior history of CMPD, while 2 patients were diagnosed with de novo AML. The clinical characteristics and laboratory features of JAK2 V617F positive patients are shown in Table 1. FLT3 internal tandem duplication, FLT3 tyrosine kinase domain mutations, AML1-ETO, CBFB-MYH, PML-RARA rearrangements or nucleophosmin mutations were not present at the time point of AML diagnosis. In the case of patient 1, thrombocytosis was present prior the diagnosis of AML, and bone marrow biopsy revealed grade 3 fibrosis at diagnosis of AML, suggesting the presence of an atypical CMPD with the coexistence of del(5q) MDS. Patient 2 had no remarkable disease in his previous medical history. Induction therapy resulted in complete hematological and cytogenetic remission with persistent JAK2 V617F positivity. 10 month later clinical features of CMPD (elevated white blood cell count, left shifted peripheral blood smear, hepatosplenomegaly) appeared. In conclusion, these two cases suggest that acute myeloid leukemia with JAK-2 V617F mutation in fact corresponds to the blastic transformation of a clinically atipical chronic myeloproliferative disorders. Clinical characteristics and laboratory features of JAK2 V617F positive patients Case Sex AML subtype Age of onset (years) FAB subtype Cytogenetic abnormality Therapy Overall Survival (months) 1 F de novo 52 M1 del(5q) DNR+ara-C, HDara-C 23 2 M de novo 65 M4 t(13;17) DNR+ara-C, HDara-C 12 3 F CMPD blastic transformation 65 M4 trisomy (1q) Supportive 18 4 M CMPD blastic transformation 70 M4 not available Supportive 3 5 M CMPD blastic transformation 71 M4 not available Supportive 6

Analysis of JAK2 V617F Mutation and Its Clinical Significance in Patients with Thrombocythemia and Other Myeloproliferative Neoplasms in Chinese

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4687-4687
Author(s):  
Yue Xu ◽  
Changxin Yin ◽  
Han He ◽  
Lingling Shu ◽  
Fuqun Wu ◽  
...  
Keyword(s):  
Polycythemia Vera ◽  
Essential Thrombocythemia ◽  
Conflicts Of Interest ◽  
Myeloproliferative Neoplasms ◽  
Jak2 V617f ◽  
Jak2 V617f Mutation ◽  
Jak2 Mutation ◽  
Western Countries ◽  
Arms Pcr ◽  
V617f Mutation

Abstract Abstract 4687 JAK2 mutation is commonly found in Philadelphia-negative myeloproliferative neoplasms (MPNs). In Western countries, this mutation is found in approximately 96 percent of people with polycythemia vera, half of individuals with essential thrombocythemia or primary myelofibrosis. We used the method of amplification refractory mutation PCR (ARMS-PCR) to investigate MPN patients in China. We focused our study on patients with essential thrombocythemia (ET). ARMS-PCR was used to detect JAK2 V617F mutation in the bone barrow (BM) or peripheral blood of 37 MPN patients, which consisting of 7 ET, 5 polycythemia vera (PV), 5 chronic myeloid leukemia (CML), 5 chronic idiopathic myelofibrosis (CIMF), as well as 15 suspected MPNs. 17 cases of JAK2 V617F mutation (45.9%) were found in 37 patients, including 4 ET (57.1%), 4 PV (80.0%), 3 CIMF (60.0%), 6 suspected MPNs (40.0%). We did not find JAK2 V617F in the patients with CML. Our results indicated that the frequency of JAK2 V617F mutation in bcr/abl-negative MPNs in Chinese is similar to that in MPN patients in Western countries. At the same time, ARMS-PCR can distinguish the mutation is heterozygous or homozygous. Most patients were heterozygous for JAK2 but only a few were homozygous. In conclusion, our study showed that JAK2 V617F mutation frequency in Chinese MPN patients is similar to that in patients with this disorder in the West. It is the major molecular genetic abnormality in bcr-abl negative MPN and it can be used for diagnosis of MPN in China. Disclosures: No relevant conflicts of interest to declare.

Leukemic blasts in transformed JAK2-V617F–positive myeloproliferative disorders are frequently negative for the JAK2-V617F mutation.

Blood ◽  
2007 ◽  
Vol 110 (1) ◽  
pp. 375-379 ◽  
Author(s):  
Alexandre Theocharides ◽  
Marjorie Boissinot ◽  
François Girodon ◽  
Richard Garand ◽  
Soon-Siong Teo ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Jak2 V617f ◽  
Myeloproliferative Disorders ◽  
Microsatellite Analysis ◽  
Jak2 V617f Mutation ◽  
Leukemic Transformation ◽  
Clonal Origin ◽  
V617f Mutation ◽  
Acute Myeloid

To study the role of the JAK2-V617F mutation in leukemic transformation, we examined 27 patients with myeloproliferative disorders (MPDs) who transformed to acute myeloid leukemia (AML). At MPD diagnosis, JAK2-V617F was detectable in 17 of 27 patients. Surprisingly, only 5 of 17 patients developed JAK2-V617F–positive AML, whereas 9 of 17 patients transformed to JAK2-V617F–negative AML. Microsatellite analysis in a female patient showed that mitotic recombination was not responsible for the transition from JAK2-V617F–positive MPD to JAK2-V617F–negative AML, and clonality determined by the MPP1 polymorphism demonstrated that the granulocytes and leukemic blasts inactivated the same parental X chromosome. In a second patient positive for JAK2-V617F at transformation, but with JAK2-V617F–negative leukemic blasts, we found del(11q) in all cells examined, suggesting a common clonal origin of MPD and AML. We conclude that JAK2-V617F–positive MPD frequently yields JAK2-V617F–negative AML, and transformation of a common JAK2-V617F–negative ancestor represents a possible mechanism.

scholarly journals Protracted Clonal Trajectory of a JAK2 V617F-Positive Myeloproliferative Neoplasm Developing during Long-Term Remission from Acute Myeloid Leukemia

2018 ◽  
Vol 2018 ◽  
pp. 1-4
Author(s):  
Stephen E. Langabeer ◽  
Karl Haslam ◽  
Maria Anne Smyth ◽  
John Quinn ◽  
Philip T. Murphy
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Myeloproliferative Neoplasms ◽  
Myeloproliferative Neoplasm ◽  
Jak2 V617f ◽  
Time Frame ◽  
Divergent Evolution ◽  
Common Precursor ◽  
Previously Treated ◽  
Acute Myeloid

Although transformation of the myeloproliferative neoplasms (MPNs) to acute myeloid leukemia (AML) is well documented, development of an MPN in patients previously treated for, and in remission from, AML is exceedingly rare. A case is described in which a patient was successfully treated for AML and in whom a JAK2 V617F-positive MPN was diagnosed after seven years in remission. Retrospective evaluation of the JAK2 V617F detected a low allele burden at AML diagnosis and following one course of induction chemotherapy. This putative chemoresistant clone subsequently expanded over the intervening seven years, resulting in a hematologically overt MPN. As AML relapse has not occurred, the MPN may have arose in a separate initiating cell from that of the AML. Alternatively, both malignancies possibly evolved from a common precursor defined by a predisposition mutation with divergent evolution into MPN through acquisition of the JAK2 V617F and AML through acquisition of different mutations. This case emphasizes the protracted time frame from acquisition of a disease-driving mutation to overt MPN and further underscores the clonal complexity in MPN evolution.

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