Bailey.Glen at 18:40, 3 November 2023

2023-11-03T18:40:52Z

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 <nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome.

Bailey.Glen: Created page with "{{Under Construction}} ==Primary Author(s)*== T. Niroshi Senaratne, UCLA TOC ==Cancer Category/Type== Myeloproliferative neoplasm (MPN) ==Cancer Sub-Classification /..."

2023-11-03T17:59:15Z

Created page with "{{Under Construction}} ==Primary Author(s)*== T. Niroshi Senaratne, UCLA __TOC__ ==Cancer Category/Type== Myeloproliferative neoplasm (MPN) ==Cancer Sub-Classification /..."

New page

{{Under Construction}}
==Primary Author(s)*==

T. Niroshi Senaratne, UCLA

__TOC__

==Cancer Category/Type==

Myeloproliferative neoplasm (MPN)

==Cancer Sub-Classification / Subtype==

Primary myelofibrosis (PMF)

==Definition / Description of Disease==

Clonal MPN characterized by proliferation of predominantly abnormal megakaryocytes and granulocytes in the bone marrow.

Prefibrotic/early PMF (pre-PMF) is associated with hypercellular bone marrow with absent or minimal reticulin fibrosis.

Overt fibrotic PMF (classic PMF) is associated with marked reticulin or collagen fibrosis in the bone marrow, often with osteosclerosis, leukoerythroblastosis in the blood, hepatomegaly, and splenomegaly.

==Synonyms / Terminology==

Chronic idiopathic myelofibrosis; myelofibrosis/sclerosis with myeloid metaplasia; agnogenic myeloid metaplasia; megakaryocytic myelosclerosis; idiopathic myelofibrosis; myelofibrosis with myeloid metaplasia; myelofibrosis as a result of myeloproliferative disease

==Epidemiology / Prevalence==

Estimated annual incidence of overt PMF is 0.5-1.5 cases per 100,000 population, with both genders nearly equally affected. Incidence of pre-PMF is not known. The age of occurrence is commonly during 60s-70s.

==Clinical Features==

As many as 30% of patients with PMF may be asymptomatic at the time of diagnosis, and are found by detection of splenomegaly, anemia, leukocytosis and/or thrombocytosis. More than 50% of patients experience constitutional symptoms.

Leukemic transformation may occur in 4-20% of patients and is associated with a poor prognosis.

==Sites of Involvement==

The bone marrow and blood are always involved. In later stages of the disease there is also extramedullary hematopoiesis, particularly in the spleen.

==Morphologic Features==

Pre-PMF: hypercellular bone marrow, with increase in neutrophils and atypical megakaryocytes

Overt PMF: reticulin or collagen fibrosis (fibrosis grades 2 or 3), often with collagen fibrosis and osteosclerosis. Most often the bone marrow is normo- or hypocellular. Atypical megakaryocytes are present in large clusters or sheets.

==Immunophenotype==

Put your text here and/or fill in the table

{| class="wikitable sortable"
|-
!Finding!!Marker
|-
|Positive (universal)||EXAMPLE CD1
|-
|Positive (subset)||EXAMPLE CD2
|-
|Negative (universal)||EXAMPLE CD3
|-
|Negative (subset)||EXAMPLE CD4
|}

==Chromosomal Rearrangements (Gene Fusions)==

{| class="wikitable sortable"
|-
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence
|-
|N/A||N/A||N/A||N/A
|-
| || || ||
|}
Note: By definition, PMF should be negative for BCR-ABL1 fusion. In very rare cases, a BCR-ABL1 rearrangement is acquired [Ref]

Balanced translocations are rare in PMF and few are recurrent. One recurrent unbalanced translocation has been described, der(6)t(1;6)(q21;p21) resulting in gain of 1q and loss of 6p [Dingli et al 2005; Djordjevic et al., 2007].

==Characteristic Chromosomal Aberrations / Patterns==

Approximately 30-42.6% of PMF cases show cytogenetic abnormalities, with more advanced cases showing increasing frequency of abnormalities. The most common are del(20q) (19-33%) and del(13q) (14-23%), with additional abnormalities including trisomy 8 (8-16%), trisomy 9 (3-14%), and abnormalities of chromosome 1 (6-28%).

Disease progression is associated with additional abnormalities, including gain of 1q (3-19%), del(5q) (3-6%), chromosome 7 abnormalities (5-10%), del(17p) and in rare cases i(17q) [Ref: Vandenberghe and Michaux, 2015 in Cancer Cytogenetics (Eds: Heim and Mitelman); see also Wassie et al 2015].

==Genomic Gain/Loss/LOH==

Put your text here and/or fill in the table

{| class="wikitable sortable"
|-
!Chromosome Number!!Gain/Loss/Amp/LOH!!Region
|-
|2||EXAMPLE Gain||EXAMPLE chr8:0-1000000
|-
|3||EXAMPLE Loss||EXAMPLE chr7:0-1000000
|}

==Gene Mutations (SNV/INDEL)==

Put your text here and/or fill in the tables

{| class="wikitable sortable"
|-
!Gene!!Mutation!!Oncogene/Tumor Suppressor/Other!!Presumed Mechanism (LOF/GOF/Other; Driver/Passenger)!!Prevalence (COSMIC/TCGA/Other)
|-
|EXAMPLE TP53||EXAMPLE R273H||EXAMPLE Tumor Suppressor||EXAMPLE LOF||EXAMPLE 20%
|}

===Other Mutations===
{| class="wikitable sortable"
|-
!Type!!Gene/Region/Other
|-
|Concomitant Mutations||EXAMPLE IDH1 R123H
|-
|Secondary Mutations||EXAMPLE Trisomy 7
|-
|Mutually Exclusive||EXAMPLE EGFR Amplification
|}

==Epigenomics (Methylation)==

Put your text here

==Genes and Main Pathways Involved==

''JAK2'' mutations result in constitutive activation of ''JAK2'' signalling. ''CALR'' and ''MPL'' mutations also result in activation of the same pathway.

==Diagnostic Testing Methods==

Initial testing for ''JAK2'' V617F mutation, followed by testing for ''CALR'' and ''MPL'' if negative. Karyotype studies as well as next generation sequencing panels for genes associated with myeloid neoplasms provide important prognostic information.

==Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)==

Since the mutations and chromosome aberrations detected in PMF can also be found in other MPN, genetic findings alone cannot be used to make the diagnosis of PMF.

There are multiple prognostic systems for PMF that take into account genetic information. In 2011 the DIPSS (Dynamic International Prognostic Scoring System for primary myelofibrosis) was updated to incorporate prognostic information from karyotype [Gangat et al 2011]. More recently, a scoring system incorporating both cytogenetic and molecular information was developed, the Mutation-Enhanced International Prognostic Score System or MIPSS70-plus [Guglielmelli et al 2018], as well as prognostic scoring system based only on genetics, the Genetically Inspired Prognostic Scoring System or GIPSS [Tefferi et al 2018a] were developed.

'''DIPSS-plus (2011)''': “Unfavorable karyotype” including complex karyotypes or the presence of one or two abnormalities including +8, −7/7q−, i(17q), inv(3), −5/5q−, 12p− or 11q23 rearrangement.

'''MIPSS70-plus (2018):''' “Very high risk (VHR) karyotype” defined as single/multiple abnormalities of -7, i(17q), inv(3)/3q21, 12p-/12p11.2, 11q-/11q23, or other autosomal trisomies not including + 8/ + 9 (e.g., +21, +19); “Favorable” including normal karyotype or sole abnormalities of 13q-, +9, 20q-, chromosome 1 translocation/duplication or sex chromosome abnormality including -Y; and “Unfavorable” including all other abnormalities. [Tefferi et al 2018b]

“HMR” (high molecular risk) mutations defined as presence of one or more mutations in ''EZH2, ASXL1, IDH1/IDH2,'' and ''SRSF2'' [Vannucchi et al 2013], subsequently updated to also include mutations in ''U2AF1'' [Tefferi et al 2018c].

'''GIPSS (2018)''': Karyotype classification using same definition as described above for MIPSS70-plus. Molecular findings associated with high risk were absence of type 1/like ''CALR'' mutations [Tefferi et al 2018e] or presence of mutations in ''ASXL1, SRSF2,'' or ''U2AF1''Q157 (''EZH2'' and ''IDH1/2'' mutations remained non-significant during multivariable analysis).

In terms of therapeutic options, the preferred option for high risk patients is allogenic stem cell transplant, while low risk patients may be followed with observation only. For intermediate risk patients, treatments including ''JAK2'' inhibitors may be used [Tefferi et al 2018d].

==Familial Forms==

Rare familial cases of bone marrow fibrosis in children have been reported but it is unclear how many of these have a myeloproliferative neoplasm [Rumi and Cazzola 2017].

==Other Information==

Put your text here

==Links==

[http://www.mipss70score.it/ Put your text here (use link icon at top of page)]

==References==
(use "Cite" icon at top of page)
<references />
===EXAMPLE Book===

#Arber DA, et al., (2017). Acute myeloid leukaemia with recurrent genetic abnormalities, 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, p129-171.

==Notes==
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome.

HAEM4:Primary Myelofibrosis (PMF) - Revision history

Bailey.Glen at 18:40, 3 November 2023

Bailey.Glen: Created page with "{{Under Construction}} ==Primary Author(s)*== T. Niroshi Senaratne, UCLA __TOC__ ==Cancer Category/Type== Myeloproliferative neoplasm (MPN) ==Cancer Sub-Classification /..."

Bailey.Glen: Created page with "{{Under Construction}} ==Primary Author(s)*== T. Niroshi Senaratne, UCLA TOC ==Cancer Category/Type== Myeloproliferative neoplasm (MPN) ==Cancer Sub-Classification /..."