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.

scholarly journals Secondary Acute Myeloid Leukemia in a One-Year-Old Girl Diagnosed with JAK2-V617F Mutation Positive Myeloproliferative Neoplasm

2014 ◽  
Vol 2014 ◽  
pp. 1-4
Author(s):  
Gary M. Woods ◽  
Rajinder P. S. Bajwa ◽  
Samir B. Kahwash ◽  
Terri Guinipero
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Poor Prognosis ◽  
Myeloproliferative Neoplasms ◽  
Pediatric Population ◽  
Myeloproliferative Neoplasm ◽  
Jak2 V617f ◽  
Secondary Acute Myeloid Leukemia ◽  
One Year ◽  
Acute Myeloid

Myeloproliferative neoplasms (MPNs) are a group of clonal disorders characterized by hyperproliferation of hematologic cell lines and have been associated with tyrosine kinase JAK2-V617F mutations. Secondary acute myeloid leukemia (sAML) is a known complication of JAK2-V617F+ MPNs and bears a poor prognosis. Although the evolution of a JAK2-V617F+ MPN to a mixed-lineage leukemia has been reported in the pediatric population, no evolutions into sAML have been described. We present a case of a one-year-old girl diagnosed with JAK2-V617F+ MPN with evolution into sAML. Despite initial morphologic remission, she eventually relapsed and succumbed to her disease.

scholarly journals Development of a myelodysplastic/myeloproliferative neoplasm-unclassifiable in a patient with acute myeloid leukemia: a case report and literature review

2021 ◽  
Vol 49 (5) ◽  
pp. 030006052110184
Author(s):  
Meifang Zhao ◽  
Jingnan Sun ◽  
Shanshan Liu ◽  
Hongqiong Fan ◽  
Yu Fu ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Myeloproliferative Neoplasms ◽  
Myeloproliferative Neoplasm ◽  
Hematologic Malignancies ◽  
Prior History ◽  
History Of ◽  
Factor Therapy ◽  
Growth Factor Therapy ◽  
Acute Myeloid

Myelodysplastic/myeloproliferative neoplasms (MDS/MPNs) are a heterogeneous group of hematologic malignancies characterized by dysplastic and myeloproliferative overlapping features in the bone marrow and blood. The occurrence of the disease is related to age, prior history of MPN or MDS, and recent cytotoxic or growth factor therapy, but it rarely develops after acute myeloid leukemia (AML). We report a rare case of a patient diagnosed with AML with t(8; 21)(q22; q22) who received systematic chemotherapy. After 4 years of follow-up, MDS/MPN-unclassifiable occurred without signs of primary AML recurrence.

scholarly journals Number of Mutations and Type of Prior Myeloproliferative Neoplasm Are Prognostic Factors in Acute Myeloid Leukemia Post Myeloproliferative Neoplasms

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2806-2806 ◽  
Author(s):  
Edmond Chiche ◽  
Sarah Bonnet ◽  
Sarah Bertoli ◽  
Andrew T Kuykendall ◽  
Lauris Gastaud ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Acute Myeloid Leukemia ◽  
Prognostic Factors ◽  
Myeloid Leukemia ◽  
Poor Prognosis ◽  
Myeloproliferative Neoplasms ◽  
Myeloproliferative Neoplasm ◽  
Induction Treatment ◽  
Calr Mutations ◽  
Acute Myeloid

Abstract BACKGROUND Post myeloproliferative neoplasms (MPN) acute myeloid leukemia (AML) occurs respectively in 1.5%, 7.0% and 11% of patients with essential thrombocytosis (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). This subgroup of AML has very poor prognosis and are often excluded from clinical trials. Therefore, only few cohorts including molecular data are available. MATERIAL AND METHODS We retrospectively collected data from 111 patients treated in four centers in France for post MPN-AML. Clinical, molecular and treatment information was available for all patients at AML and MPN stages. DNA was extracted from samples at diagnosis of MPN chronic phase, at diagnosis of AML phase and after induction treatment. JAK2-V617F mutations were identified by qPCR (Ipsogen® MutaQuant kit, Qiagen, Germany), MPL-W515L/K mutations were identified by PCR (Ipsogen® MutaScreen kit, Qiagen, Germany) and CALR mutations were identified by conventional sequencing (Applied Biosystems, 3500Genetic Analyzer). NGS on 36 genes using Ampliseq librairy and Ion Proton sequencing (Thermofisher, Waltham, MA, USA) were performed in 96/111 patients. Overall response rate (ORR) was defined by complete remission (CR), CR with incomplete hematologic recovery (CRi), partial remission (PR) and stable disease (SD). Overall survival (OS) was calculated from the date of AML diagnosis to the date of death or last follow-up. All statistical analyses were performed using SPSS v.22 software (IBM SPSS Statistics). RESULTS 111 patients treated for post MPN-AML were retrospectively included in this study. Sex ratio M/F was 54%/46%. Median age at AML diagnosis was 66 years (28-89, range). Cytogenetic categories were favorable, intermediate and adverse in 2 (2%), 51 (46%) and 47 (42%) patients, respectively. 25/111 (23%) patients had a monosomal karyotype (MK). Median number of additional mutations excluding from JAK2/MPL/CALR mutations was 2 (0-6, range). The most frequent additional mutations were TP53 (23%), ASXL1 (17%), TET2 (13%), SRSF2 (10%), DNMT3A (8%), SF3B1 (8%) and RUNX1 (8%). Only 2 patients were mutated for NPM1 and 2 and 4 patients were FLT3-ITD and FLT3-TKD, respectively. Prior MPN were PV, ET and PMF in 20%, 34% and 46% of patients, respectively. First line treatment was intensive chemotherapy (IC) for 61 (55%) patients, hypomethylating agents (HMA) for 10 (9%) or other treatments including best supportive care, cytoreduction for the other ones. 24/111 (22%) underwent to ASCT. ORR was 54% (with 30/71 (42%) in CR/CRi) in patients treated by IC or HMA. We did not identify factors predicting a higher rate of CR/CRi. OS was 12 months [6-18] and was not influenced by transplant, cytogenetic categories or by the type and allele frequencies of JAK2/CALR/MPL mutations. OS was significantly longer in the group treated with HMA as compared to IC (10 versus 46 months, respectively, p=0.006); in patients with prior PV as compared to ET or MF (26 months [0-57] versus 10 months [7-13] versus 10 months [4-16] respectively, p=0.07) and in patients with presence of additional mutations other than JAK2/CALR/MPL (5 months [0-12] versus 46 months [32-60] in 38 patients without mutation versus 58 patients with presence of at least one mutation, respectively, p=0.04). By multivariate analysis, only presence of additional mutations was predictive for OS with a hazard ratio (HR) = 0.42 [0.18-0.97] (p=0.04). Finally, we followed the VAFs of JAK2 in seven patients before and after IC. We observed in 2 patients an increase of JAK2 clone correlated with CR whereas no variation of VAFs was associated with absence of CR. CONCLUSIONS In conclusion, we confirmed the poor prognosis of post MPN AML. Classical AML prognostic factors were not validated in our cohort. We identified the presence of mutations other than JAK2/MPL/CALR as the main prognostic factor whereas post-PV AML appeared to do better than post-ET and post-PMF AML. The very poor result of IC with or without ASCT highlights the need to develop specific clinical trials in this subgroup of AML. Disclosures Kuykendall: Celgene: Honoraria; Janssen: Consultancy. Sallman:Celgene: Research Funding, Speakers Bureau. Cluzeau:CELGENE: Consultancy; MENARINI: Consultancy; JAZZ PHARMA: Consultancy.

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.

Deletions of the Transcription Factor Ikaros in Myeloproliferative Neoplasms at Transformation to Acute Myeloid Leukemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 435-435 ◽  
Author(s):  
Roland Jäger ◽  
Heinz Gisslinger ◽  
Tiina Berg ◽  
Francesco Passamonti ◽  
Mario Cazzola ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Myeloproliferative Neoplasms ◽  
Clonal Evolution ◽  
Chronic Phase ◽  
Jak2 V617f ◽  
Leukemic Transformation ◽  
Genetic Changes ◽  
Oncogenic Mutations ◽  
Acute Myeloid

Abstract Abstract 435 Transformation to acute myeloid leukemia (AML) is a major complication of myeloproliferative neoplasms (MPNs). Although clinical prognostic factors have been defined such as age, severe anemia, elevated white blood cell count with a high proportion of immature myeloid cells and a high number of circulating CD34+ cells, there is little knowledge of the genetic changes leading to leukemic transformation in MPN. To gain insight into these genetic changes, we studied 12 patients with post-MPN leukemia using Affymetrix SNP 6.0 microarrays. Acquired genetic lesions were detected in 10 patients. Beyond well described frequent events like 9pUDP, chromosome 7p deletions (del7p) emerged as a novel recurrent defect in this patient group. Mapping of the minimal deleted region of del7p by combining microarray, copy number and loss of heterozygosity analysis resulted in a minimal deleted region of 0.25 Mb in size, restricted to the IKZF1 gene. IKZF1 is encoding the transcription factor Ikaros, which is known to have a pleiotropic function in the regulation of hematopoiesis, as well as crucial involvement in hematopoietic malignancies, primarily of the lymphoid lineages. Based on the observation of 16.7% (2 out of 12) of post-MPN leukemia patients carrying an IKZF1 deletion, we further screened a chronic phase MPN patient cohort from Vienna for the defect and found 1 out of 235 informative patients carrying an IKZF1 deletion. Thus, deletion of IKZF1 exhibited statistically significant clustering with post-MPN leukemia when compared to chronic phase MPN (P=0.0063). To validate these results in an independent patient cohort, we screened 20 post-MPN leukemic and 156 chronic phase MPN patients from Pavia for loss of IKZF1, and found 4 and 1 positive patients, respectively (P=0.0006). Taking these two cohorts together, IKZF1 deletions could be found in 0.5% of chronic MPN patients and 18.8% of post-MPN leukemic patients, showing statistically significant association with post-MPN leukemia (P<0.0001). We could define haploinsufficiency as mechanism of IKZF1 tumor suppressor inactivation, since IKZF1 exon sequencing of del7p patients did not show any mutations on the non-deleted allele of IKZF1 and IKZF1 mRNA could be detected in del7p patients. In order to characterize the role of IKZF1 deletion in clonal expansion, we monitored oncogenic mutation and deletion burdens in granulocytes of two del7p patients in serial samples over time. In both patients, one being positive for JAK2-V617F and the other for MPL-W515L, increased IKZF1 deletion burden was detected as a late event after the acquisition of oncogenic mutations. We also examined the hematopoietic progenitors of a del7p patient by genotyping individual BFU-E and CFU-GM colonies for defects detected in granulocytes. IKZF1 deletion was found to be a late defect in the clonal evolution of MPN, occurring after oncogenic mutations such as JAK2-V617F and chromosomal aberrations such as del13q. In murine hematopoietic progenitor cells, sh-RNA induced deficiency for Ikzf1 resulted in cytokine hypersensitivity in vitro. Based on these data we can conclude that IKZF1 deletion does not induce arrest in myeloid differentiation, it is a late genetic event in the clonal evolution of MPN and represents an important step in the leukemic transformation of a subpopulation of MPN patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Myeloid Sarcoma Involving Kidneys: From Diagnosis to Treatment. Case Report and Literature Review

2020 ◽  
Vol 14 (1) ◽  
Author(s):  
Francesca Guidotti ◽  
Angelo Gardellini ◽  
Maddalena Feltri ◽  
Michelle Zancanella ◽  
Vittoria Saccà ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Hematological Malignancy ◽  
Myeloproliferative Neoplasm ◽  
Jak2 V617f ◽  
Obstructive Nephropathy ◽  
Hematological Tumors ◽  
Collecting System ◽  
Acute Myeloid

Myeloid sarcomas (MS) are rare extramedullary hematological tumors which generally occur during the natural course of acute myeloid leukemia or chronic myeloid leukemia. Rarely, their onset precedes peripheral blood and bone marrow manifestations of disease. Common sites of involvement are skin, bone, soft tissue, lymph nodes, reproductive or digestive organs, and central nervous system.Herein, we report the case of a 72-year-old man affected by JAK2 V617F mutated myeloproliferative neoplasm who developed MS involving collecting system of both kidneys. MS and MS-related obstructive nephropathy were the first signs of the acute evolution of a known chronic hematological malignancy, preceding by some weeks the onset of leukocytosis. 

scholarly journals A Paraneoplastic Syndrome Characterized by Extremity Swelling with Associated Inflammatory Infiltrate Heralds Aggressive Transformation of Myelodysplastic Syndromes/Myeloproliferative Neoplasms to Acute Myeloid Leukemia: A Case Series

2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
James K. Mangan ◽  
Selina M. Luger
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndromes ◽  
Myeloid Leukemia ◽  
Myeloproliferative Neoplasms ◽  
Intensive Therapy ◽  
Myeloproliferative Neoplasm ◽  
Case Series ◽  
Disease Status ◽  
Inflammatory Syndrome ◽  
Acute Myeloid

There has been a long history of reports describing a variety of paraneoplastic phenomena associated with myelodysplastic syndromes, particularly those with autoimmune manifestations. We report here a series of patients with an antecedent myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN) that underwent aggressive transformation to acute myeloid leukemia (AML). In each case, the transformation to AML was preceded by an inflammatory syndrome characterized by unilateral extremity swelling and an associated inflammatory skin infiltrate, as well as other signs of inflammation, including profound hyperferritinemia without evidence of a hemophagocytic syndrome. We suggest that such an inflammatory syndrome may herald aggressive transformation of MDS/MPN to AML. Patients with known MDS/MPN who present with these features may benefit from early bone marrow examination to assess disease status. Early intervention with corticosteroids in select patients may result in improvement or resolution of the symptoms and permit intensive therapy for AML to be delivered.

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