HAEM5:Myeloid/lymphoid neoplasm with FGFR1 rearrangement: Difference between revisions

[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]]

<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Myeloid/Lymphoid Neoplasms with FGFR1 Rearrangement]].

 

==Cancer Category / Type==

 

Myeloid/lymphoid neoplasms  

 

==Cancer Sub-Classification / Subtype==

 

Myeloid/lymphoid neoplasms with eosinophilia and gene rearrangement

 

 

Myeloid/lymphoid neoplasms with ''FGFR1'' rearrangement are a heterogenous group of aggressive neoplasms with translocations involving the fibroblast growth factor receptor 1(''FGFR1)'' tyrosine kinase gene on chromosome 8p11-12<ref name=":2">{{Cite journal|last=Jackson|first=Courtney C.|last2=Medeiros|first2=L. Jeffrey|last3=Miranda|first3=Roberto N.|date=2010|title=8p11 myeloproliferative syndrome: a review|url=http://www.sciencedirect.com/science/article/pii/S0046817709004067|journal=Human Pathology|volume=41|issue=4|pages=461–476|doi=10.1016/j.humpath.2009.11.003|issn=0046-8177}}</ref>.  The neoplastic cells derive from a pluripotent haematopoietic stem cell and may be immature or mature<ref name=":0">Bain BJ, et al., (2017). Myeloid/lymphoid neoplasms with FGFR1 rearrangement in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p77-78.</ref>. Cases can present as a myeloproliferative neoplasm or as acute myeloid leukaemia, T- or B-lymphoblastic leukaemia/lymphoma or mixed-phenotype acute leukaemia. T-cell lymphoblastic lymphoma/leukemia is common, frequently with eosinophilia, and subsequently rapidly transforms into acute myeloid leukaemia. 

Coexistence of atypical chronic myeloid leukaemia, ''BCR-ABL1''-negative, with t(8;19)(p11.2;q13.1) and ''KIT'' D816V-positive systemic mastocytosis with an associated haematological neoplasm has been reported <ref name=":6">{{Cite journal|last=Duckworth|first=Christina B|last2=Zhang|first2=Linsheng|last3=Li|first3=Shiyong|date=2014|title=Systemic mastocytosis with associated myeloproliferative neoplasm with t(8;19)(p12;q13.1) and abnormality of FGFR1: report of a unique case|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3925931/|journal=International Journal of Clinical and Experimental Pathology|volume=7|issue=2|pages=801–807|issn=1936-2625|pmc=3925931|pmid=24551307}}</ref>.

|'''Signs and Symptoms'''

|EXAMPLE Asymptomatic (incidental finding on complete blood counts)

 

 

 

|'''Laboratory Findings'''

|EXAMPLE Cytopenias

 

!Finding!!Marker

|Positive (universal)||EXAMPLE CD1

|Positive (subset)||EXAMPLE CD2

|-

|Negative (universal)||EXAMPLE CD3

|Negative (subset)||EXAMPLE CD4

|}

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Immunophenotypic analysis is not helpful in chronic phase disease. However, in lymphoblastic leukemia/lymphoma and in acute myeloid transformation, immunophenotypic analysis is important to distinguish the lineage origins, such as B- or T- lineage, or myeloid lineage <ref name=":0" />. Please refer to the above section "Morphologic Features".

 

</blockquote>

==Chromosomal Rearrangements (Gene Fusions)==

 

Put your text here and fill in the table

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

!Diagnostic Significance (Yes, No or Unknown)

!Prognostic Significance (Yes, No or Unknown)

|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)

|Yes

|No

|Yes

|EXAMPLE

 

|}

<blockquote class='blockedit'>{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}

|Most common, around 40% <ref>{{Cite journal|last=Popovici|first=C.|last2=Adelaide|first2=J.|last3=Ollendorff|first3=V.|last4=Chaffanet|first4=M.|last5=Guasch|first5=G.|last6=Jacrot|first6=M.|last7=Leroux|first7=D.|last8=Birnbaum|first8=D.|last9=Pebusque|first9=M.-J.|date=1998|title=Fibroblast growth factor receptor 1 is fused to FIM in stem-cell myeloproliferative disorder with t(8;13)(p12;q12)|url=http://www.pnas.org/cgi/doi/10.1073/pnas.95.10.5712|journal=Proceedings of the National Academy of Sciences|language=en|volume=95|issue=10|pages=5712–5717|doi=10.1073/pnas.95.10.5712|issn=0027-8424|pmc=PMC20444|pmid=9576949}}</ref><ref>{{Cite journal|last=Cross|first=Nicholas C. P.|last2=Goldman|first2=John M.|last3=Jennings|first3=Barbara A.|last4=Hernandez|first4=Jesus M.|last5=Gonçalves|first5=Cristina|last6=Aguiar|first6=Ricardo C. T.|last7=Macdonald|first7=Donald H. C.|last8=Chase|first8=Andrew|last9=Kulkarni|first9=Shashikant|date=1998|title=Consistent Fusion of ZNF198 to the Fibroblast Growth Factor Receptor-1 in the t(8;13)(p11;q12) Myeloproliferative Syndrome|url=https://ashpublications.org/blood/article/92/5/1735/247374/Consistent-Fusion-of-ZNF198-to-the-Fibroblast|journal=Blood|language=en|volume=92|issue=5|pages=1735–1742|doi=10.1182/blood.V92.5.1735|issn=0006-4971}}</ref><ref>{{Cite journal|last=Smedley|first=D|date=1998|title=The t(8;13)(p11;q11-12) rearrangement associated with an atypical myeloproliferative disorder fuses the fibroblast growth factor receptor 1 gene to a novel gene RAMP|url=https://academic.oup.com/hmg/article-lookup/doi/10.1093/hmg/7.4.637|journal=Human Molecular Genetics|volume=7|issue=4|pages=637–642|doi=10.1093/hmg/7.4.637}}</ref><ref name=":3">{{Cite journal|last=Xiao|first=Sheng|last2=Nalabolu|first2=Srinivasa R.|last3=Aster|first3=Jon C.|last4=Ma|first4=Junli|last5=Abruzzo|first5=Lynne|last6=Jaffe|first6=Elaine S.|last7=Stone|first7=Richard|last8=Weissman|first8=Sherman M.|last9=Hudson|first9=Thomas J.|date=1998|title=FGFR1 is fused with a novel zinc-finger gene, ZNF198, in the t(8;13) leukaemia/lymphoma syndrome|url=http://www.nature.com/articles/ng0198-84|journal=Nature Genetics|language=en|volume=18|issue=1|pages=84–87|doi=10.1038/ng0198-84|issn=1061-4036}}</ref><ref>{{Cite journal|last=Bain|first=Barbara J.|last2=Fletcher|first2=Sarah H.|date=2007-08|title=Chronic Eosinophilic Leukemias and the Myeloproliferative Variant of the Hypereosinophilic Syndrome|url=http://dx.doi.org/10.1016/j.iac.2007.06.001|journal=Immunology and Allergy Clinics of North America|volume=27|issue=3|pages=377–388|doi=10.1016/j.iac.2007.06.001|issn=0889-8561}}</ref><ref name=":2" />

<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:

* Gene Mutations (SNV/INDEL)}}

Unlike myeloid/lymphoid neoplasms with ''[[Myeloid/Lymphoid Neoplasms with PDGFRA Rearrangement#cite ref-:0 1-4|PDGFRA]]'' or ''PDGFRB'' rearrangement, the prognosis for this ''FGFR1'' associated entity is poor even for patient in the chronic phase, due to the high incidence of transformation. There is no established tyrosine kinase inhibitor therapy for myeloproliferative neoplasms with ''FGFR1'' rearrangement. Midostaurin (PKC412) was reported to be effective in one case <ref>{{Cite journal|last=Chen|first=J.|last2=DeAngelo|first2=D. J.|last3=Kutok|first3=J. L.|last4=Williams|first4=I. R.|last5=Lee|first5=B. H.|last6=Wadleigh|first6=M.|last7=Duclos|first7=N.|last8=Cohen|first8=S.|last9=Adelsperger|first9=J.|date=2004|title=PKC412 inhibits the zinc finger 198-fibroblast growth factor receptor 1 fusion tyrosine kinase and is active in treatment of stem cell myeloproliferative disorder|url=http://www.pnas.org/cgi/doi/10.1073/pnas.0404438101|journal=Proceedings of the National Academy of Sciences|language=en|volume=101|issue=40|pages=14479–14484|doi=10.1073/pnas.0404438101|issn=0027-8424|pmc=PMC521956|pmid=15448205}}</ref>, and interferon has induced cytogenetic response in several cases <ref name=":1" /> <ref>{{Cite journal|last=Holmes|first=A L|last2=Raper|first2=R N|last3=Heilig|first3=J S|date=1998|title=Genetic analysis of Drosophila larval optic nerve development.|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1460051/|journal=Genetics|volume=148|issue=3|pages=1189–1201|issn=0016-6731|pmc=1460051|pmid=9539434}}</ref>. Nevertheless, haematopoietic stem cell transplantation should be considered even for patients in chronic phase.

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

!Chr #!!Gain / Loss / Amp / LOH!!Minimal Region Genomic Coordinates [Genome Build]!!Minimal Region Cytoband

!Diagnostic Significance (Yes, No or Unknown)

!Prognostic Significance (Yes, No or Unknown)

!Therapeutic Significance (Yes, No or Unknown)

!Notes

|EXAMPLE

 

|EXAMPLE Loss

|EXAMPLE

 

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

 

|Yes

|Yes

|No

|EXAMPLE

 

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).

|EXAMPLE

 

|EXAMPLE Gain

|EXAMPLE

 

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

 

|No

|No

|No

|EXAMPLE

 

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

==Characteristic Chromosomal Patterns==

!Diagnostic Significance (Yes, No or Unknown)

!Prognostic Significance (Yes, No or Unknown)

!Therapeutic Significance (Yes, No or Unknown)

!Notes

|EXAMPLE

 

|Yes

|EXAMPLE:

 

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

<blockquote class='blockedit'>{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}

A variety of translocations involving 8p11 breakpoint. Secondary cytogenetic abnormalities also occur, most commonly trisomy 21 <ref name=":0" />.

==Gene Mutations (SNV / INDEL)==

!Gene; Genetic Alteration!!'''Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)'''!!'''Prevalence (COSMIC /  TCGA / Other)'''!!'''Concomitant Mutations'''!!'''Mutually Exclusive Mutations'''

!'''Diagnostic Significance (Yes, No or Unknown)'''

!Prognostic Significance (Yes, No or Unknown)

!Therapeutic Significance (Yes, No or Unknown)

!Notes

|EXAMPLE: TP53; Variable LOF mutations

EXAMPLE:

 

EGFR; Exon 20 mutations

 

EXAMPLE: BRAF; Activating mutations

|EXAMPLE: TSG

|EXAMPLE: 20% (COSMIC)

 

EXAMPLE: 30% (add Reference)

|EXAMPLE: IDH1 R123H

|EXAMPLE: EGFR amplification

|}

Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table.'')</span>

|EXAMPLE: BRAF and MAP2K1; Activating mutations

|EXAMPLE: MAPK signaling

|EXAMPLE: Increased cell growth and proliferation

|EXAMPLE: CDKN2A; Inactivating mutations

|EXAMPLE: Cell cycle regulation

|EXAMPLE: Unregulated cell division

|EXAMPLE:  KMT2C and ARID1A; Inactivating mutations

|EXAMPLE:  Histone modification, chromatin remodeling

|EXAMPLE:  Abnormal gene expression program

<blockquote class='blockedit'>{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}

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