PDGFRB-Associated Chronic Eosinophilic Leukemia

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This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/condition/pdgfrb-associated-chronic-eosinophilic-leukemia

PDGFRB-associated chronic eosinophilic leukemia is a type of cancer of blood-forming cells.

genetic conditions

1. Introduction

It is characterized by an elevated number of white blood cells called eosinophils in the blood. These cells help fight infections by certain parasites and are involved in the inflammation associated with allergic reactions. However, these circumstances do not account for the increased number of eosinophils in PDGFRB-associated chronic eosinophilic leukemia. Some people with this condition have an increased number of other types of white blood cells, such as neutrophils or mast cells, in addition to eosinophils. People with this condition can have an enlarged spleen (splenomegaly) or enlarged liver (hepatomegaly). Some affected individuals develop skin rashes, likely as a result of an abnormal immune response due to the increased number of eosinophils.

2. Frequency

The exact prevalence of PDGFRB-associated chronic eosinophilic leukemia is unknown. For unknown reasons, males are up to nine times more likely than females to develop PDGFRB-associated chronic eosinophilic leukemia.

3. Causes

PDGFRB-associated chronic eosinophilic leukemia is caused by genetic rearrangements that join part of the PDGFRB gene with part of another gene. At least 20 genes have been found that fuse with the PDGFRB gene to cause PDGFRB-associated chronic eosinophilic leukemia. The most common genetic abnormality in this condition results from a rearrangement (translocation) of genetic material that brings part of the PDGFRB gene on chromosome 5 together with part of the ETV6 gene on chromosome 12, creating the ETV6-PDGFRB fusion gene.

The PDGFRB gene provides instructions for making a protein that plays a role in turning on (activating) signaling pathways that control many cell processes, including cell growth and division (proliferation). The ETV6 gene provides instructions for making a protein that turns off (represses) gene activity. This protein is important in development before birth and in regulating blood cell formation. The protein produced from the ETV6-PDGFRB fusion gene, called ETV6/PDGFRβ, functions differently than the proteins normally produced from the individual genes. Like the normal PDGFRβ protein, the ETV6/PDGFRβ fusion protein turns on signaling pathways. However, the fusion protein does not need to be turned on to be active, so the signaling pathways are constantly turned on (constitutively activated). The fusion protein is unable to repress gene activity regulated by the normal ETV6 protein, so gene activity is increased. The constitutively active signaling pathways and abnormal gene activity increase the proliferation and survival of cells.

When the ETV6-PDGFRB fusion gene mutation occurs in cells that develop into blood cells, the growth of eosinophils (and occasionally other blood cells, such as neutrophils and mast cells) is poorly controlled, leading to PDGFRB-associated chronic eosinophilic leukemia. It is unclear why eosinophils are preferentially affected by this genetic change.

4. Inheritance

PDGFRB-associated chronic eosinophilic leukemia is not inherited and occurs in people with no history of the condition in their families. Chromosomal rearrangements that lead to a PDGFRB fusion gene are somatic mutations, which are mutations acquired during a person's lifetime and present only in certain cells. The somatic mutation occurs initially in a single cell, which continues to grow and divide, producing a group of cells with the same mutation (a clonal population).

5. Other Names for This Condition

atypical Philadelphia-negative chronic myeloid leukemia
chronic myelomonocytic leukemia
chronic myeloproliferative disorder with eosinophilia
clonal eosinophilia with chronic myeloproliferative disorder
primary eosinophilia with chronic myeloproliferative disorder

References

Apperley JF, Gardembas M, Melo JV, Russell-Jones R, Bain BJ, Baxter EJ, Chase A, Chessells JM, Colombat M, Dearden CE, Dimitrijevic S, Mahon FX, Marin D,Nikolova Z, Olavarria E, Silberman S, Schultheis B, Cross NC, Goldman JM.Response to imatinib mesylate in patients with chronic myeloproliferativediseases with rearrangements of the platelet-derived growth factor receptor beta.N Engl J Med. 2002 Aug 15;347(7):481-7.
Arefi M, García JL, Peñarrubia MJ, Queizán JA, Hermosín L, López-Corral L,Megido M, Giraldo P, de las Heras N, Vanegas RJ, Gutiérrez NC, Hernández-RivasJM. Incidence and clinical characteristics of myeloproliferative neoplasmsdisplaying a PDGFRB rearrangement. Eur J Haematol. 2012 Jul;89(1):37-41. doi:10.1111/j.1600-0609.2012.01799.x.
Chang H, Chuang WY, Sun CF, Barnard MR. Concurrent acute myeloid leukemia and T lymphoblastic lymphoma in a patient with rearranged PDGFRB genes. Diagn Pathol.2012 Feb 22;7:19. doi: 10.1186/1746-1596-7-19.
Cross NC, Reiter A. Fibroblast growth factor receptor and platelet-derivedgrowth factor receptor abnormalities in eosinophilic myeloproliferativedisorders. Acta Haematol. 2008;119(4):199-206. doi: 10.1159/000140631.
Galimberti S, Ferreri MI, Simi P, Azzarà A, Baratè C, Fazzi R, Cecconi N,Cervetti G, Guerrini F, Petrini M. Platelet-derived growth factor beta receptor(PDGFRB) gene is rearranged in a significant percentage of myelodysplasticsyndromes with normal karyotype. Br J Haematol. 2009 Dec;147(5):763-6. doi:10.1111/j.1365-2141.2009.07878.x.
Gotlib J. Eosinophilic myeloid disorders: new classification and noveltherapeutic strategies. Curr Opin Hematol. 2010 Mar;17(2):117-24. doi:10.1097/MOH.0b013e3283366c70. Review.
Gotlib J. World Health Organization-defined eosinophilic disorders: 2012update on diagnosis, risk stratification, and management. Am J Hematol. 2012Sep;87(9):903-14. doi: 10.1002/ajh.23293.
Haferlach C, Bacher U, Schnittger S, Alpermann T, Zenger M, Kern W, Haferlach T. ETV6 rearrangements are recurrent in myeloid malignancies and are frequentlyassociated with other genetic events. Genes Chromosomes Cancer. 2012Apr;51(4):328-37. doi: 10.1002/gcc.21918.
Noel P. Eosinophilic myeloid disorders. Semin Hematol. 2012 Apr;49(2):120-7.doi: 10.1053/j.seminhematol.2012.01.008. Review.
Zhou MH, Gao L, Jing Y, Xu YY, Ding Y, Wang N, Wang W, Li MY, Han XP, Sun JZ, Wang LL, Yu L. Detection of ETV6 gene rearrangements in adult acute lymphoblasticleukemia. Ann Hematol. 2012 Aug;91(8):1235-43. doi: 10.1007/s00277-012-1431-4.

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Rita Xu

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Table of Contents

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1. Introduction

2. Frequency

3. Causes

4. Inheritance

5. Other Names for This Condition

References

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1. Introduction

2. Frequency

3. Causes

The Genes and Chromosomes Associated with PDGFRB-Associated Chronic Eosinophilic Leukemia

4. Inheritance

5. Other Names for This Condition

References