Myeloid/Lymphoid Neoplasms with Eosinophilia and TK Fusion Genes, Version 3.2021, NCCN Clinical Practice Guidelines in Oncology

Gerds, Aaron T.; Gotlib, Jason; Bose, Prithviraj; Deininger, Michael W.; Dunbar, Andrew; Elshoury, Amro; George, Tracy I.; Gojo, Ivana; Gundabolu, Krishna; Hexner, Elizabeth O.; Hobbs, Gabriela; Jain, Tania; Kuykendall, Andrew; McMahon, Brandon; Mohan, Sanjay; Oh, Stephen T.; Pardanani, Animesh; Podoltsev, Nikolai A.; Ranheim, Erik A.; Rein, Lindsay; Salit, Rachel B.; Snyder, David S.; Stein, Brady L.; Talpaz, Moshe; Thota, Swapna; Vachhani, Pankit; Wadleigh, Martha; Walsh, Katherine; Ward, Dawn C.; Bergman, Mary Anne; Sundar, Hema

doi:10.6004/jnccn.2020.0042

Cited by 26 publications

(41 citation statements)

References 107 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This points out that while this mutation usually is demonstrable by routine cytogenetics [3], the diagnosis can be quite difficult to make. Lee has noted that the breakpoints for both involved genes can be highly variable [16].…”

Section: Discussionmentioning

confidence: 99%

“…Lee has noted that the breakpoints for both involved genes can be highly variable [16]. Thus, specific probes for this variant, PCR, FISH, flow cytometry, cytogenetics and NGS may be required when investigating potential cases [3,[16][17][18]. Patients with therapy-induced myelodysplastic syndrome/acute myeloblastic leukemia (tMDS/AML) have not, to our knowledge, been reported to harbor these fusions, though a study is currently looking for them (NCT03943394).…”

Section: Discussionmentioning

confidence: 99%

“…As this type of analysis is carried out more often, we may find more cases of these variants than we are currently aware of. United States National Comprehensive Care Network guidelines suggest JAK2 inhibitors (ruxolitinib or federatinib) or clinical trial participation for myelodysplasia in chronic phase with consideration for early allogeneic stem cell transplantation, which has produced long-term survivors in a number of cases [3,17].…”

Section: Discussionmentioning

confidence: 99%

“…Less well known, however, are a variety of uncommon translocations and rearrangements involving JAK2 that can also activate these pathways. Rearrangements have been reported involving PDGFRA, PDGFRB, FGFR1, PCM1, ETV6, BCR, PAX-5, SEC31A, TEL, FLT3 and ABL1 [3][4][5][6][7]. These variants affect a wide variety of hematopoietic cell lines and can lead to malignancy in any of them [7,8].…”

mentioning

confidence: 99%

“…These variants affect a wide variety of hematopoietic cell lines and can lead to malignancy in any of them [7,8]. They are now classified by the WHO as "myeloid/lymphoid neoplasms with eosinophilia and TK fusion genes" [3,9]. Of note, rearrangements with PDGFRA and PDGFRB have been reported to respond well to imatinib [10][11][12].…”

mentioning

confidence: 99%

See 4 more Smart Citations

Treatment of PCM1-JAK2 Fusion Tyrosine Kinase Gene-Related Acute Lymphoblastic Leukemia with Stem Cell Transplantation

Kaplan¹,

Jin

Scanlan

et al. 2021

Future Rare Dis.

View full text Add to dashboard Cite

PCM1-JAK2 fusion mutations are rare variants that activate a tyrosine kinase leading to a variety of neoplasms that can involve any hematologic cell line. They most often present as myelodysplasia (MPD) and can demonstrate prominent eosinophilia and/or erythrodysplasia. Transformation to acute leukemia is often seen, as is de novo leukemia. Lymphomas have also been reported. The diagnosis can often be made with routine cytogenetic analysis but specific probes and detailed next generation sequencing may be necessary. JAK2 inhibitors are active in MPD as is stem cell transplantation. Transplantation has occasionally been successful in leukemic phase as well. The current case highlights both the difficulties in diagnosis as well as the second successful treatment of MPD, transformed into acute lymphoblastic leukemia.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Treatment of PCM1-JAK2 Fusion Tyrosine Kinase Gene-Related Acute Lymphoblastic Leukemia with Stem Cell Transplantation

Kaplan¹,

Jin

Scanlan

et al. 2021

Future Rare Dis.

View full text Add to dashboard Cite

show abstract

Involvement of the JAK‐STAT pathway in the molecular landscape of tyrosine kinase fusion‐negative hypereosinophilic syndromes: A nationwide CEREO study

Groh,

Fenwarth,

Labro

et al. 2024

American J Hematol

View full text Add to dashboard Cite

We investigated using a custom NGS panel of 149 genes the mutational landscape of 64 consecutive adult patients with tyrosine kinase fusion‐negative hypereosinophilia (HE)/hypereosinophilic syndrome (HES) harboring features suggestive of myeloid neoplasm. At least one mutation was reported in 50/64 (78%) patients (compared to 8/44 (18%) patients with idiopathic HE/HES/HEUS used as controls; p < .001). Thirty‐five patients (54%) had at least one mutation involving the JAK‐STAT pathway, including STAT5B (n = 18, among which the hotspot N642H, n = 13), JAK1 (indels in exon 13, n = 5; V658F/L, n = 2), and JAK2 (V617F, n = 6; indels in exon 13, n = 2). Other previously undescribed somatic mutations were also found in JAK2, JAK1, STAT5B, and STAT5A, including three patients who shared the same STAT5A V707fs mutation and features consistent with primary polycythemia. Nearly all JAK‐STAT mutations were preceded by (or associated with) myelodysplasia‐related gene mutations, especially in RNA‐splicing genes or chromatin modifiers. In multivariate analysis, neurologic involvement (hazard ratio [HR] 4.95 [1.87–13.13]; p = .001), anemia (HR 5.50 [2.24–13.49]; p < .001), and the presence of a high‐risk mutation (as per the molecular international prognosis scoring system: HR 6.87 [2.39–19.72]; p < .001) were independently associated with impaired overall survival. While corticosteroids were ineffective in all treated JAK‐STAT‐mutated patients, ruxolitinib showed positive hematological responses including in STAT5A‐mutated patients. These findings emphasize the usefulness of NGS for the workup of tyrosine kinase fusion‐negative HE/HES patients and support the use of JAK inhibitors in this setting. Updated classifications could consider patients with JAK‐STAT mutations and eosinophilia as a new “gene mutated‐entity” that could be differentiated from CEL, NOS, and idiopathic HES.

show abstract

T cell phenotype and lack of eosinophilia are not uncommon in extramedullary myeloid/lymphoid neoplasms with ETV6::FLT3 fusion: a case report and review of the literature

Schoelinck,

Gervasoni,

Guillermin

et al. 2023

Virchows Arch

View full text Add to dashboard Cite

Myeloid/Lymphoid Neoplasms with Eosinophilia and TK Fusion Genes, Version 3.2021, NCCN Clinical Practice Guidelines in Oncology

Cited by 26 publications

References 107 publications

Treatment of PCM1-JAK2 Fusion Tyrosine Kinase Gene-Related Acute Lymphoblastic Leukemia with Stem Cell Transplantation

Treatment of PCM1-JAK2 Fusion Tyrosine Kinase Gene-Related Acute Lymphoblastic Leukemia with Stem Cell Transplantation

Involvement of the JAK‐STAT pathway in the molecular landscape of tyrosine kinase fusion‐negative hypereosinophilic syndromes: A nationwide CEREO study

T cell phenotype and lack of eosinophilia are not uncommon in extramedullary myeloid/lymphoid neoplasms with ETV6::FLT3 fusion: a case report and review of the literature

Contact Info

Product

Resources

About