HAEM5:Chronic eosinophilic leukaemia: Difference between revisions

{{DISPLAYTITLE:Chronic eosinophilic leukaemia}}

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==Primary Author(s)*==

==Clinical Features==

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|'''Signs and Symptoms'''

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|'''Laboratory Findings'''

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CEL, NOS is sometimes discovered incidentally in otherwise asymptomatic individuals. In other instances, patients experience constitutional symptoms including weight loss, night sweats, fever, fatigue, cough, angioedema, muscle pain, pruritis and diarrhea. Endomyocardial fibrosis with ensuing restrictive cardiomegaly is known to precipitate the most severe clinical presentation. Scarring of the bicuspid and mitral valves can lead to valvular regurgitation and intracardiac thrombi formation which may embolize to the brain and other organs. Cardiac failure may also occur. Peripheral neuropathy, central nervous system dysfunction and pulmonary symptoms due to lung infiltration as well as rheumatological findings are also common. [1]

!Finding!!Marker

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!Notes

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|Yes

|No

|Yes

The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference).

No single or specific genetic abnormality has been identified in CEL, NOS. Rearrangement of PDGFRA, PDGFRB, or FGFR1 excludes the diagnosis of CEL, NOS. PCM1-JAK2, ETV6-JAK2, or BCR-JAK2 are also specifically excluded. [1] Three unique cases of myeloid/lymphoid neoplasm with eosinophilia have shown ''FLT3'' rearrangement: one with t(13;14)(q12;q32)/''TRIP11-FLT3'' rearrangement, and two with ''ETV6-FLT3''. Eosinophilia and ''FLT3'' rearrangement typically shows myeloproliferative neoplasms, most frequently CEL, NOS, and T-ALL. [5] A unique case of CEL,NOS with a novel fusion gene between exon 22 of GCC2 and exon 12 of PDGFRB was detected and confirmed by PCR in a 54 year old man presenting with cough and dyspnea. [6]  

!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence

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* Chromosomal Rearrangements (Gene Fusions)

* Individual Region Genomic Gain/Loss/LOH

==Individual Region Genomic Gain / Loss / LOH==

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!Notes

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7

chr7:1- 159,335,973 [hg38]

chr7

|Yes

|No

Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference).

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8

chr8:1-145,138,636 [hg38]

chr8

|No

|No

Common recurrent secondary finding for t(8;21) (add reference).

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!Chromosome Number!!Gain/Loss/Amp/LOH!!Region

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==Characteristic Chromosomal Patterns==

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!Notes

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Co-deletion of 1p and 18q

|No

|No

See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).

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A recurrent karyotypic abnormality typically observed in myeloid disorders such as gain of chromosome 8, loss of chromosome 7 or isochromosome 17q supports a diagnosis as well as the presence of a translocation. [1] [1] Morsia et al demonstrated cytogenetic abnormalities in 15 of 17 (88.2%) patients diagnosed with CEL, NOS including trisomy 8 (n = 4), and complex karyotype (n = 3). [4]  

==Gene Mutations (SNV / INDEL)==

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!Notes

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EGFR; Exon 20 mutations

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JAK2 mutations have been identified, however mutations in ASXL1, TET2 and EZH2 appear to be common. [1] The study by Morsia et al. of 17 CEL patients demonstrated two patients each with 13q, 20q deletion, and chromosome 1 abnormalities, one patient with monosomy 7 and one with 3q deletion. All seven patients with NGS studies harbored one or more mutations; ''ASXL1'' (42.9%); ''IDH1'' (28.6%), and one each (14.3%) with ''TP53'', ''SRSF2'', ''SH2B3'', ''STAT5B'', ''KDM6A'' and ''NF1'' mutations. [4] A novel ''JAK2'' exon 13 insertion/deletion mutant has been identified and described by Patel et al. in a patient fulfilling diagnostic criteria for both PV and CEL. This study demonstrated that JAK2ex13InDel bears mechanistic resemblance to JAK2V617F but can activate STAT5 in the absence of βc family cytokines IL-3, IL-5, and GM-CSF, potentially promoting eosinophilic differentiation. [7] Keleman et al. discussed STAT5B mutations as reported in four cases: two cases of CEL, NOS; one case of CMML with eosinophilia; and one case of MDS with eosinophilia, respectively. While the presence of a STAT5B N642H mutation may be a potential marker of chronic eosinophilic neoplasms, similar mutations have been described in nonclonal HE and may not be independently sufficient to establish a diagnosis of CEL, NOS. [8]  

!Gene!!Mutation!!Oncogene/Tumor Suppressor/Other!!Presumed Mechanism (LOF/GOF/Other; Driver/Passenger)!!Prevalence (COSMIC/TCGA/Other)

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!Type!!Gene/Region/Other

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==Genes and Main Pathways Involved==

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!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome

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