Atypical Phenotype and Treatment Response Pattern in a Patient with FIP1L1-PDGFRα Mutation

2018 ◽  
Vol 140 (2) ◽  
pp. 67-70 ◽  
Author(s):  
Mihir Bikhchandani ◽  
Ryan Johnson ◽  
Bertrand Tuan ◽  
Ayalew Tefferi
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Myeloproliferative Neoplasm ◽  
Myeloproliferative Disorders ◽  
Second Line ◽  
Imatinib Resistance ◽  
Hypercellular Marrow ◽  
Atypical Phenotype ◽  
Acute Myeloid

Myeloproliferative disorders with eosinophilia may possess the FIP1L1-PDGFRα gene rearrangement. When this rearrangement is present, imatinib usually results in complete remission. In rare cases of imatinib resistance, there is poor evidence guiding second-line therapy. We present the case of a 71-year-old male who presented with abdominal discomfort, fevers, and leukocytosis with eosinophilia. The patient was diagnosed with a myeloproliferative neoplasm with eosinophilia and FIP1L1-PDGFRα rearrangement after a bone marrow evaluation revealed hypercellular marrow with eosinophilia and fluorescence in situ hybridization identified the FIP1L1-PDGFRα rearrangement. The patient was successfully treated with imatinib. Within months he relapsed and converted into acute myeloid leukemia. The patient was then treated with ponatinib which induced and maintained clinical and hematological remission for 2 months. That ponatinib briefly induced remission in our patient with acute myeloid leukemia arising from a myeloproliferative neoplasm with eosinophilia and FIP1L1-PDGFRα fusion may merit exploration of ponatinib as a potential second-line treatment option for this patient population. This is especially true given the lack of reliable therapies in instances of imatinib resistance.

scholarly journals Targeting the epichaperome as an effective precision medicine approach in a novel PML-SYK fusion acute myeloid leukemia

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Mayumi Sugita ◽  
David C. Wilkes ◽  
Rohan Bareja ◽  
Kenneth W. Eng ◽  
Sarah Nataraj ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Stem Cell Transplant ◽  
Myeloproliferative Neoplasm ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
Target Engagement ◽  
Cell Level ◽  
Evaluation And Monitoring ◽  
Acute Myeloid

AbstractThe epichaperome is a new cancer target composed of hyperconnected networks of chaperome members that facilitate cell survival. Cancers with an altered chaperone configuration may be susceptible to epichaperome inhibitors. We developed a flow cytometry-based assay for evaluation and monitoring of epichaperome abundance at the single cell level, with the goal of prospectively identifying patients likely to respond to epichaperome inhibitors, to measure target engagement, and dependency during treatment. As proof of principle, we describe a patient with an unclassified myeloproliferative neoplasm harboring a novel PML-SYK fusion, who progressed to acute myeloid leukemia despite chemotherapy and allogeneic stem cell transplant. The leukemia was identified as having high epichaperome abundance. We obtained compassionate access to an investigational epichaperome inhibitor, PU-H71. After 16 doses, the patient achieved durable complete remission. These encouraging results suggest that further investigation of epichaperome inhibitors in patients with abundant baseline epichaperome levels is warranted.

scholarly journals De novo adult acute myeloid leukemia with two new mutations in juxtatransmembrane domain of the FLT3 gene: a case report

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Ismael F. Alarbeed ◽  
Abdulsamad Wafa ◽  
Faten Moassass ◽  
Bassel Al-Halabi ◽  
Walid Al-Achkar ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Chromosomal Abnormalities ◽  
Molecular Genetic ◽  
Type A ◽  
Chemotherapeutic Treatment ◽  
Acute Myeloid ◽  
New Mutations

Abstract Background Approximately 30% of adult acute myeloid leukemia (AML) acquire within fms-like tyrosine kinase 3 gene (FLT3) internal tandem duplications (FLT3/ITDs) in their juxtamembrane domain (JMD). FLT3/ITDs range in size from three to hundreds of nucleotides, and confer an adverse prognosis. Studies on a possible relationship between of FLT3/ITDs length and clinical outcomes in those AML patients were inconclusive, yet. Case presentation Here we report a 54-year-old Arab male diagnosed with AML who had two FLT3-ITD mutations in addition to NPM1 mutation. Cytogenetic approaches (banding cytogenetics) and fluorescence in situ hybridization (FISH) using specific probes to detect translocations t(8;21), t(15;17), t(16;16), t(12;21), and deletion del(13q)) were applied to exclude chromosomal abnormalities. Molecular genetic approaches (polymerase chain reaction (PCR) and the Sanger sequencing) identified a yet unreported combination of two new mutations in FLT3-ITDs. The first mutation induced a frameshift in JMD, and the second led to a homozygous substitution of c.1836T>A (p.F612L) also in JMD. Additionally a NPM1 type A mutation was detected. The first chemotherapeutic treatment was successful, but 1 month after the initial diagnosis, the patient experienced a relapse and unfortunately died. Conclusions To the best of our knowledge, a combination of two FLT3-ITD mutations in JMD together with an NPM1 type A mutation were not previously reported in adult AML. Further studies are necessary to prove or rule out whether the size of these FLT3-ITDs mutations and potential other double mutations in FLT3-ITD are correlated with the observed adverse outcome.

scholarly journals DNA damage in acute myeloid leukemia patients of Northern Mexico

2017 ◽  
Author(s):  
Martha I. Dávila-Rodríguez ◽  
Elva I. Cortés-Gutiérrez ◽  
Roberto Hernández-Valdés ◽  
Karla Guzmán-Cortés ◽  
Rosa E. De León-Cantú ◽  
...  
Keyword(s):  
Dna Damage ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Fluorescent In Situ Hybridization ◽  
Control Group ◽  
Repair Pathway ◽  
Blood Leukocytes ◽  
Northern Mexico ◽  
Acute Myeloid

The purpose of this study was to evaluate DNA damage in the whole genome of peripheral blood leukocytes from patients with acute myeloid leukemia (AML) compared with a control group using DNA breakage detection-fluorescent in situ hybridization (DBD-FISH). Our results suggest that the DNA damage detected in patients with newly diagnosed AML was similar to that observed for the controls; this might be explained by the stimulation of a repair pathway by the pathogenesis itself. These findings indicate that inhibiting the repair pathway could be proposed to enhance the efficacy of chemotherapy.

scholarly journals Early Fluorescence in situ Hybridization Assessment during Acute Myeloid Leukemia Induction Chemotherapy

2018 ◽  
Vol 139 (3) ◽  
pp. 171-175
Author(s):  
Robert Schneidewend ◽  
Paul Hosking ◽  
Ruta Brazauskas ◽  
Jess Peterson ◽  
Carlie Beaudin ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Acute Myeloid

A novel syndrome of radiation-associated acute myeloid leukemia involving AML1 gene translocations

Blood ◽  
2000 ◽  
Vol 95 (12) ◽  
pp. 4011-4013 ◽  
Author(s):  
Robert Hromas ◽  
Rinah Shopnick ◽  
Hani George Jumean ◽  
Charles Bowers ◽  
Marileila Varella-Garcia ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
World War Ii ◽  
Myeloid Leukemia ◽  
World War ◽  
Nuclear Explosions ◽  
Radiation Induced ◽  
Aml1 Gene ◽  
High Level ◽  
Acute Myeloid

Abstract AML1 is a transcriptional activator that is essential for normal hematopoietic development. It is the most frequent target for translocations in acute leukemia. We recently identified 3 patients in whom pancytopenia developed almost 50 years after high-level radiation exposure from nuclear explosions during or after World War II. In all 3 patients, acute myeloid leukemia (AML) eventually developed that had similar characteristics and clinical courses. Cytogenetics from the 3 patients revealed a t(1;21)(p36;q22), a t(18;21)(q21;q22), and a t(19;21)(q13.4;q22). By fluorescent in situ hybridization (FISH), all 3 translocations disrupted the AML1 gene. Two of theseAML1 translocations, the t(18;21) and the t(19;21), have not been reported previously. It is possible that the AML1 gene is a target for radiation-induced AML.

scholarly journals Prognostic Value of Metaphase-Fluorescence In Situ Hybridization in Follow-up of Patients With Acute Myeloid Leukemia in Remission

Blood ◽  
1997 ◽  
Vol 89 (9) ◽  
pp. 3330-3334 ◽  
Author(s):  
Wa'el El-Rifai ◽  
Tapani Ruutu ◽  
Erkki Elonen ◽  
Liisa Volin ◽  
Sakari Knuutila
Keyword(s):  
Acute Myeloid Leukemia ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Myeloid Leukemia ◽  
Allogeneic Bone Marrow Transplantation ◽  
Leukemic Cells ◽  
Allogeneic Bone ◽  
Abnormal Cells ◽  
Acute Myeloid

Abstract The presence of residual leukemic cells was studied using metaphase-fluorescence in situ hybridization (FISH) in 22 patients with acute myeloid leukemia treated with chemotherapy only or chemotherapy followed by allogeneic bone marrow transplantation. The patients were followed up during their complete remission (CR) for 4 to 108 months (median, 21 months). A total of 88 BM samples was studied. In most of the samples more than 1,000 metaphase cells were analyzed. Residual leukemic cells were detected in 9 of 22 patients (41%). All patients who had an increasing and/or persisting level of abnormal cells in two or more subsequent samples or whose initial samples contained more than 1% of abnormal cells relapsed with one exception, in whom the later subsequent samples showed disappearance of abnormal cells. The time span before the first positive sample seems to be insignificant with regard to the outcome of relapse. Absence or single occurrence of abnormal cells followed by their disappearance was in agreement with CR in all the cases (16 patients). Our results indicate that metaphase-FISH is a reliable tool in the quantitation of residual leukemic cells and provides valuable prognostic information for patients with AML.

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