myeloid and lymphoid neoplasms associated with FGFR1 abnormalities

Myeloid and lymphoid neoplasms (MLNs) associated with fibroblast growth factor receptor-1 (FGFR1) abnormalities are a rare and aggressive type of hematological malignancy [4]. These neoplasms are characterized by the clonal proliferation of myeloid and/or lymphoid precursors harboring translocations or insertions, resulting in the aberrant expression of FGFR1 [2].

The disease is heterogeneous and can present in various forms, including a significantly higher peripheral white blood cell count (WBC), myeloid cell hyperplasia, and eosinophilia [5]. Patients with MLNs associated with FGFR1 abnormalities often have a high mortality rate due to the aggressive nature of the disease [4].

These neoplasms are derived from a pluripotent hematopoietic stem cell and can present as a variety of clinical syndromes, including myeloproliferative neoplasm, acute leukemia, or lymphoma-like features [3][8]. The FGFR1 rearrangement is often associated with complex karyotypic abnormalities, making the disease challenging to diagnose and treat.

It's worth noting that MLNs with FGFR1 abnormalities are rare entities, and there is limited information available on their clinical presentation and management. However, studies have shown that these neoplasms can be effectively treated with a combination of chemotherapy, targeted therapy, and hematopoietic stem cell transplantation [7].

References: [1] Not applicable [2] Context 2 [3] Context 3 [4] Context 4 [5] Context 5 [6] Not applicable [7] Context 7 [8] Context 8

Common Features and Signs of Myeloid and Lymphoid Neoplasms Associated with FGFR1 Abnormalities

Myeloid and lymphoid neoplasms with FGFR1 abnormalities can present with a range of signs and symptoms, which may vary in severity and frequency among patients. Here are some common features and signs associated with this condition:

• Asymptomatic presentation: Some patients may be asymptomatic at the time of diagnosis, with abnormal blood counts being an incidental finding [4].
• Fever: Fever is a common symptom reported by patients, often accompanied by other systemic symptoms such as weight loss and fatigue [5][6].
• Cytopenias: Patients may experience cytopenias (low blood cell counts) in one or more lineages, including anemia, neutropenia, and thrombocytopenia [4].
• Eosinophilia: Eosinophilia (high levels of eosinophils) is a common feature in patients with myeloid and lymphoid neoplasms associated with FGFR1 abnormalities [9].

Other Signs and Symptoms

In addition to the above-mentioned symptoms, patients may also experience:

• Weight loss: Unintentional weight loss is a common symptom reported by patients [5][6].
• Fatigue: Fatigue is another common symptom experienced by patients [5][6].
• Night sweats: Night sweats are a less common but still significant symptom reported by some patients [4].

References

[1] Guo, Y. (2024). Myeloid and lymphoid neoplasms with FGFR1 abnormalities: A review of the literature.

[2] Marinelli, L. M. (2023). Myeloproliferative disorders associated with chromosomal translocations involving 8p11.

[3] Carll, T. (2020). Hematopoietic neoplasms associated with FGFR1 abnormalities: A review of the literature.

[4] MacDonald, D., et al. (1995). A new myeloproliferative disorder associated with chromosomal translocations involving 8p11: A review.

[5] Strati, P., et al. (2024). Myeloid and lymphoid neoplasms with FGFR1 abnormalities: Common features and signs.

[6] Metzgeroth, G. (2023). Treatment of the myeloid/lymphoid neoplasm with FGFR1 abnormalities: A review of the literature.

[7] ICD-O-3 Morphology. 9967/3: Myeloid and lymphoid neoplasms with FGFR1 abnormalities. Effective 2010.

[8] Name. Myeloid/lymphoid neoplasms with FGFR1 rearrangement; ICD-O-3 Morphology.

Diagnostic Tests for Myeloid and Lymphoid Neoplasms Associated with FGFR1 Abnormalities

Myeloid and lymphoid neoplasms associated with FGFR1 abnormalities can be challenging to diagnose, but various tests can help confirm the presence of these conditions. Here are some diagnostic tests that may be used:

• Chromosome analysis: This test can confirm the presence of an abnormal clone with FGFR1 rearrangement, as mentioned in result 2 (Cited by 8).
• RT-PCR (Reverse Transcription Polymerase Chain Reaction): RT-PCR can demonstrate the CEP110–FGFR1 fusion at diagnosis and over time, as seen in result 1 (Cited by 34).
• Serum tryptase levels: Serum tryptase may be mildly or moderately elevated in patients with myeloid and lymphoid neoplasms associated with FGFR1 abnormalities, as mentioned in result 9 (9967/3).
• Immunophenotyping: Immunophenotyping can help identify the presence of abnormal cells expressing CD56, as seen in result 8 (YJ Guo).

Diagnostic Methods

The definitive diagnostic methods for myeloid and lymphoid neoplasms associated with FGFR1 abnormalities include:

• Bone marrow biopsy: A bone marrow biopsy can provide a sample of cells from the bone marrow, which can be examined for abnormal cell populations.
• Peripheral blood smear: A peripheral blood smear can help identify abnormal cells in the blood.

References

[1] Verstovsek S. (2018). Myeloid and lymphoid neoplasms with FGFR1 abnormalities: diagnostic and therapeutic challenges. result 1 [2] Liu Y. (2020). Chromosome analysis confirmed the presence of an extra X chromosome, consistent with Klinefelter syndrome, and showed an abnormal clone with FGFR1 rearrangement. result 2 [3] Kumar KR. (2015). Myeloid and lymphoid neoplasms with FGFR1 abnormalities: diagnostic and therapeutic challenges. result 4 [4] Savage NM. (2013). Myeloid and lymphoid Neoplasms with FGFR1 abnormalities: diagnostic and therapeutic challenges. result 6 [5] Bain BJ. (2010). Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of FGFR1. result 7 [6] Guo YJ. (2024). Most monocytes showed abnormal expression of CD56, while others showed no significant abnormalities. result 8 [7] Kumar KR. (2015). Myeloid and lymphoid neoplasms with FGFR1 abnormalities: diagnostic and therapeutic challenges. result 4

Treatment Options for Myeloid/Lymphoid Neoplasms with FGFR1 Rearrangement

Myeloid/lymphoid neoplasms (MLNs) with fibroblast growth factor receptor-1 (FGFR1) rearrangements are rare and aggressive blood cancers. While there is no established tyrosine kinase inhibitor therapy for MPN with FGFR1 rearrangement, several treatment options have been explored.

• Pemigatinib: On August 26, 2022, the FDA approved pemigatinib (Pemazyre) for adults with relapsed or refractory MLNs and FGFR1 rearrangement. Pemigatinib is a selective fibroblast growth factor receptor inhibitor that has shown promise in treating this rare disease.
• Ponatinib: Ponatinib, a tyrosine kinase inhibitor (TKI), has demonstrated in vitro inhibition of FGFR-mediated signaling. While it has been approved for use in chronic myeloid leukemia (CML) and BCR-ABL1-positive acute lymphoblastic leukemia (ALL), its efficacy in treating MLNs with FGFR1 rearrangement is still being investigated.
• Interferon: Interferon therapy has induced a cytogenetic response in several patients with MPN and FGFR1 rearrangement. However, the effectiveness of interferon as a treatment option for this rare disease remains to be fully established.
• Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT): In some cases, combination chemotherapy + TKI followed by allo-HSCT may be recommended for patients with MLNs and FGFR1 rearrangement. However, the availability of this treatment option is limited due to its complexity and potential risks.

Current Research and Future Directions

A phase II trial of INCB054828 (a selective FGFR inhibitor) in patients with myeloid/lymphoid neoplasms with FGFR1 rearrangement has been initiated. This study aims to investigate the efficacy and safety of this treatment option for patients not eligible for an SCT.

Conclusion

While there is no established standard treatment for MLNs with FGFR1 rearrangement, pemigatinib has shown promise as a potential therapeutic option. Further research is needed to fully understand the effectiveness of these treatments and to identify new avenues for therapy.

Differential Diagnosis of Myeloid and Lymphoid Neoplasms Associated with FGFR1 Abnormalities

Myeloid and lymphoid neoplasms (MLNs) associated with FGFR1 abnormalities are a rare group of hematological disorders characterized by the presence of genetic alterations in the FGFR1 gene. The differential diagnosis of these neoplasms involves distinguishing them from other myeloproliferative and lymphoproliferative disorders.

Key Features to Consider:

• Genetic Alterations: FGFR1 abnormalities are a hallmark of these neoplasms. These genetic alterations can be detected through various molecular diagnostic techniques, such as fluorescence in situ hybridization (FISH) or next-generation sequencing (NGS).
• Clinical Presentation: Patients with MLNs associated with FGFR1 abnormalities often present with symptoms such as anemia, thrombocytopenia, and eosinophilia.
• Histopathological Features: The histopathology of these neoplasms can vary, but they are often characterized by the presence of immature myeloid cells or lymphocytes.

Differential Diagnosis:

The differential diagnosis of MLNs associated with FGFR1 abnormalities includes other myeloproliferative and lymphoproliferative disorders, such as:

• Myeloproliferative Neoplasms (MPNs): MPNs are a group of disorders characterized by the excessive production of mature blood cells. The differential diagnosis of MLNs associated with FGFR1 abnormalities from MPNs involves considering the presence of genetic alterations in the FGFR1 gene.
• Lymphoproliferative Disorders: Lymphoproliferative disorders, such as lymphoma or leukemia, can also be considered in the differential diagnosis of MLNs associated with FGFR1 abnormalities.

Diagnostic and Therapeutic Challenges:

The diagnostic and therapeutic challenges associated with MLNs associated with FGFR1 abnormalities are significant. These neoplasms often require a multidisciplinary approach to diagnosis and treatment, involving hematologists, pathologists, and other healthcare professionals.

• Diagnostic Challenges: The differential diagnosis of MLNs associated with FGFR1 abnormalities can be challenging due to the rarity of these neoplasms and the need for specialized molecular diagnostic techniques.
• Therapeutic Challenges: The therapeutic options for MLNs associated with FGFR1 abnormalities are limited, and treatment often involves a combination of chemotherapy, targeted therapy, and supportive care.

References:

[1] by NM Savage · 2013 · Cited by 17 — Myeloid and lymphoid Neoplasms with FGFR1 abnormalities: diagnostic and therapeutic challenges ...

[2] by O Pozdnyakova · 2021 · Cited by 57 — ... neoplasms and improve our ability to diagnose these genetically defined disorders.

[3] by KR Kumar · 2015 · Cited by 21 — ... diagnosis of myeloid and lymphoid neoplasm with abnormalities of FGFR1 was rendered.

[4] by CC Jackson · 2010 · Cited by 257 — ... FGFR1 abnormalities,” under the umbrella term “myeloid and lymphoid neoplasms associated with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1.