Difference between revisions of "HAEM5:Hairy cell leukaemia"

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Haematolymphoid Tumours (WHO Classification, 5th ed.)

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editContent Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification

This page was converted to the new template on 2023-12-07. The original page can be found at HAEM4:Hairy Cell Leukemia.

(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use HUGO-approved gene names and symbols (italicized when appropriate), HGVS-based nomenclature for variants, as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column to a table, click within the table and select the > symbol that appears to be given options. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see Author_Instructions and FAQs as well as contact your Associate Editor or Technical Support)

Primary Author(s)*

Michael Lack, DO, Shivani Golem, PhD FACMG

WHO Classification of Disease

Structure	Disease
Book	Haematolymphoid Tumours (5th ed.)
Category	B-cell lymphoid proliferations and lymphomas
Family	Mature B-cell neoplasms
Type	Splenic B-cell lymphomas and leukaemias
Subtype(s)	Hairy cell leukaemia

Definition / Description of Disease

Hairy cell leukemia (HCL) is a rare indolent neoplasm of B-cell origin seen mostly in adults
Name derives from the the hair-like projections of the cytoplasm that surround the cells
Hairy cells most closely resemble mature lymphoid cells
Marked splenomegaly and marrow infiltration result in left flank discomfort, fatigue, and susceptibility to infections
Most respond well to monotherapy with a purine analog or interferon alpha

Synonyms / Terminology

Leukemic reticuloendotheliosis

Epidemiology / Prevalence

Incidence (age adjusted) ~ 0.3/100,000
2% of lymphoid leukemias
Median age: 58 years, rarely in patients in their 20s
Males:Females: 4:1
Whites >> Blacks
78% to 92% 5yr survival

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^[1]^[2]

Clinical Features

Signs and Symptoms	Asymptomatic (incidental finding on complete blood counts) B-symptoms (weight loss, fever, night sweats) Fatigue Splenic enlargement and discomfort Recurrent infections Lymphadenopathy (rare)
Laboratory Findings	Pancytopenia (monocytopenia is characteristic) Lymphocytosis (low level)

editv4:Clinical Features

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Signs & Symptoms

Asymptomatic (incidental finding on complete blood counts)

B-symptoms (weight loss, fever, night sweats)

Fatigue

LUQ pain (splenomegaly)

Lymphadenopathy (uncommon)

Laboratory findings

Cytopenias

Monocytopenia

Lymphocytosis (low level)

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^[1]^[3]

Sites of Involvement

Spleen (red pulp)
Bone marrow
Liver
Blood (small number)

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^[1]^[3]

Morphologic Features

Small lymphoid cells
Abundant pale blue-grey lacey cytoplasm
Ovoid nuclei ± indentation or folding
Inconspicuous nucleoli
Circumferential hairy projections (smear preparations)
"Fried egg" appearance of cells (tissue sections)
Marrow (reticulin) fibrosis

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^[1]^[3]

Immunophenotype

Finding	Marker
Positive (B-cell lineage markersl)	CD19, CD20 (bright), CD22, PAX5, FMC7, sIg (bright, monoclonal)
Positive	CD200 (bright), CD11c, CD103, CD123, CD25, CD72, annexin‐A1, BRAF V600E, phospho-ERK
Negative	CD5, CD10 (10-20% may be positive), CD23, CD27

editv4:Immunophenotype

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Finding Marker

Positive (B-cell lineage markers) CD19, CD20 (bright), CD22, PAX5, FMC7, sIg (bright, monoclonal)

Positive CD200 (bright), CD11c, CD103, CD123, CD25, CD72, annexin‐A1, BRAF V600E, phospho-ERK

Negative CD5, CD10 (10-20% may be positive), CD23, CD27

editUnassigned References

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^[1]^[3]

Chromosomal Rearrangements (Gene Fusions)

No consistent gene fusions
Single case report of IGH-BRAF fusion positive, BRAF p.Val600Glu mutation negative HCL^[4]
Single case report of IGH-CCND1 fusion positive, BRAF p.Val600Glu mutation positive HCL^[5]

editv4:Chromosomal Rearrangements (Gene Fusions)

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No consistent gene fusions

Single case report of IGH-BRAF fusion positive, BRAF p.Val600Glu mutation negative HCL^[4]

Single case report of IGH-CCND1 fusion positive, BRAF p.Val600Glu mutation positive HCL^[5]

editv4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).

Please incorporate this section into the relevant tables found in:
Chromosomal Rearrangements (Gene Fusions)

Individual Region Genomic Gain/Loss/LOH

Characteristic Chromosomal Patterns

Gene Mutations (SNV/INDEL)

Alteration Clinical Significance Note

BRAF p.Val600Glu Predictive* vemurafenib for 2nd line; vemurafenib ± rituximab for 3rd line (NCCN, v 1.2020, pg. HCL-A)^[6]

BRAF p.Val600Glu Diagnostic May be useful when immunophenotype is equivocal; Excludes HCLv

MAP2K1 Predictive Certain mutations may confer sensitivity to ERK inhibitors

IGHV4-34 utilization Predictive Reduced response to purine analogs^[7]

IGHV4-34 utilization Prognostic Less favorable prognosis^[7]

*Not all BRAF mutations confer sensitivity to BRAF inhibitors, even if they are activating mutations^[8].

Individual Region Genomic Gain / Loss / LOH

chromosome^[9]^[10]	Alteration	Consequence	Prevalence
14q22-32	Heterozygous deletion	Uncertain	33%
7q	Heterozygous deletion	LOH of BRAF p.Val600Glu	9-21%
13q	Deletion	Loss of RB1, miR-15a, and miR-16-1	6%
5	Gain	Uncertain	9-15%

editv4:Genomic Gain/Loss/LOH

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Recurrent gains and losses were found to be absent in HCLs from Chinese patients^[11]

chromosome^[9]^[10] Alteration Consequence Prevalence

14q22-32 Heterozygous deletion Uncertain 33%

7q Heterozygous deletion LOH of BRAF p.Val600Glu 9-21%

13q Deletion Loss of RB1, miR-15a, and miR-16-1 6%

5 Gain Uncertain 9-15%

Characteristic Chromosomal Patterns

IGHV4-34 (Immunoglobulin heavy chain variable segment) utilization is seen only in 10%^[7] of HCL but has predictive and prognostic implications^[12].

editv4:Characteristic Chromosomal Aberrations / Patterns

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IGHV4-34 (Immunoglobulin heavy chain variable segment) utilization is seen only in 10%^[7] of HCL but has predictive and prognostic implications^[12].

Gene Mutations (SNV / INDEL)

Gene^‡	Oncogene/Tumor Suppressor/Other	Presumed Mechanism (LOF/GOF/Other)	Prevalence^[1]
BRAF	Oncogene	GOF	70-100%*
MAP2K1	Oncogene	GOF	0-22%*
TP53	Tumor Suppressor	LOF	2-28%
KLF2	Oncogene/Tumor Suppressor	context dependent^[13]	13-16%
CDKN1B	Tumor Suppressor	LOF	10-16%
ARID1A	Tumor Suppressor	LOF	4-5%
KMT2C	Tumor Suppressor	LOF	15%
CREBBP	Tumor Suppressor	LOF	5-6%

^‡Specific mutations in these genes can be found in cBioPortal and COSMIC.

*The WHO states that BRAF p.Val600Glu is detected in virtually all cases and notes that the classification of B-cell leukemias that are immunophenotypically and morphologically classified as HCL but lack BRAF activating mutations (but instead have MAP2K1 activating mutations and use the IGHV4-34 gene segment) is uncertain. These seem to be more similar molecularly and clinically to HCLv.

BRAF and MAP2K1 activating mutations are mutually exclusive
BRAF p.Val600Glu and MAP2K1 account for the primary oncogene drivers in the majority of HCL (~95%)
BRAF p.Val600Glu (p.V600E) accounts for the majority of BRAF mutations, but other have been reported^[14]
HCLs that utilize the IGVH4-34 segment lack BRAF p.Val600Glu mutations^[15] and instead harbor MAP2K1 mutations in most cases^[16]

editv4:Gene Mutations (SNV/INDEL)

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Gene^‡ Oncogene/Tumor Suppressor/Other Presumed Mechanism
(LOF/GOF/Other)
Prevalence^[1]

BRAF Oncogene GOF 70-100%*

MAP2K1 Oncogene GOF 0-22%*

TP53 Tumor Suppressor LOF 2-28%

KLF2 Oncogene/Tumor Suppressor context dependent^[13] 13-16%

CDKN1B Tumor Suppressor LOF 10-16%

ARID1A Tumor Suppressor LOF 4-5%

KMT2C Tumor Suppressor LOF 15%

CREBBP Tumor Suppressor LOF 5-6%

^‡Specific mutations in these genes can be found in cBioPortal and COSMIC.
*The WHO states that BRAF p.Val600Glu is detected in virtually all cases and notes that the classification of B-cell leukemias that are immunophenotypically and morphologically classified as HCL but lack BRAF activating mutations (but instead have MAP2K1 activating mutations and use the IGHV4-34 gene segment) is uncertain. These seem to be more similar molecularly and clinically to HCLv.

BRAF and MAP2K1 activating mutations are mutually exclusive

BRAF p.Val600Glu and MAP2K1 account for the primary oncogene drivers in the majority of HCL (~95%)

BRAF p.Val600Glu (p.V600E) accounts for the majority of BRAF mutations, but other have been reported^[14]

HCLs that utilize the IGVH4-34 segment lack BRAF p.Val600Glu mutations^[15] and instead harbor MAP2K1 mutations in most cases^[16]

Epigenomic Alterations

Altered epigenetic regulation is expected due to alterations in KMT2C and ARID1A in a subset of HCLs
- KMT2C is a histone methyltransferase
- ARID1A is a SWI/SNF family member

Genes and Main Pathways Involved

Molecular feature	Pathway	Pathophysiologic outcome
BRAF & MAP2K1 activating mutations (IGH-BRAF fusion, 1 report^[4])	MAPK signaling	Increased cell growth and proliferation
CDKN1B inactivating mutations (IGH-CCND1 fusion, 1 report^[5])	Cell cycle regulation	Unregulated cell division
KMT2C & ARID1A inactivating mutaitons	Histone modification, chromatin remodeling	Abnormal gene expression program

editv4:Genes and Main Pathways Involved

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Molecular feature Pathway Pathophysiologic outcome

BRAF & MAP2K1 activating mutations
(IGH-BRAF fusion, 1 report^[4])
MAPK signaling Increased cell growth and proliferation

CDKN1B inactivating mutations
(IGH-CCND1 fusion, 1 report^[5])
Cell cycle regulation Unregulated cell division

KMT2C & ARID1A inactivating mutaitons Histone modification, chromatin remodeling Abnormal gene expression program

Genetic Diagnostic Testing Methods

Morphology and immunophenotyping (IHC or flow cytometry) are adequate for diagnosis in nearly all cases
BRAF p.Val600Glu testing may be useful diagnostically in rare situations where clinicopathologic findings are equivocal
BRAF p.Val600Glu may be detected by IHC using a mutant-specific antibody^[17]^[18] or various molecular methods (NGS, real-time PCR, massARRAY, etc.)
The mutant-specific antibody does not detect other BRAF mutations
BRAF p.Val600Glu and Non-p.Val600Glu mutations and MAP2K1 mutations can be interrogated with NGS in a single assay^[1]
IGHV4-34 utilization can be detected by NGS

Familial Forms

Familial association has been reported in several case reports
Some linked to various HLA type^[19]
Others to familial occupation^[20]

Additional Information

N/A

Links

References

(use the "Cite" icon at the top of the page) (Instructions: Add each reference into the text above by clicking on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference.)

↑ ^1.0 ^1.1 ^1.2 ^1.3 ^1.4 ^1.5 ^1.6 ^1.7 Maitre, Elsa; et al. (2019). "Hairy cell leukemia: 2020 update on diagnosis, risk stratification, and treatment". American Journal of Hematology. 94 (12): 1413–1422. doi:10.1002/ajh.25653. ISSN 1096-8652. PMID 31591741.
↑ Lr, Teras; et al. (2016). "2016 US Lymphoid Malignancy Statistics by World Health Organization Subtypes". PMID 27618563.
↑ ^3.0 ^3.1 ^3.2 ^3.3 Grever, Michael R.; et al. (2017). "Consensus guidelines for the diagnosis and management of patients with classic hairy cell leukemia". Blood. 129 (5): 553–560. doi:10.1182/blood-2016-01-689422. ISSN 0006-4971. PMC 5290982. PMID 27903528.CS1 maint: PMC format (link)
↑ ^4.0 ^4.1 ^4.2 ^4.3 Thompson, Ella R.; et al. (2020). "Detection of an IGH-BRAF fusion in a patient with BRAF Val600Glu negative hairy cell leukemia". Leukemia & Lymphoma: 1–3. doi:10.1080/10428194.2020.1753045. ISSN 1029-2403. PMID 32319330 Check |pmid= value (help).
↑ ^5.0 ^5.1 ^5.2 ^5.3 Rahman, Zaid Abdel; et al. (2020). "Hairy cell leukemia with CCND1/IGH fusion gene and BRAF V600E mutation". Leukemia Research Reports. 13: 100197. doi:10.1016/j.lrr.2020.100197. ISSN 2213-0489. PMC 7096740 Check |pmc= value (help). PMID 32257795 Check |pmid= value (help).
↑ National Comprehensive Cancer Network (January 2020). "NCCN Clinical Practice Guidelines in Oncology: Hairy Cell Leukemia" (PDF).CS1 maint: display-authors (link)
↑ ^7.0 ^7.1 ^7.2 ^7.3 Arons, Evgeny; et al. (2009). "VH4-34+ hairy cell leukemia, a new variant with poor prognosis despite standard therapy". Blood. 114 (21): 4687–4695. doi:10.1182/blood-2009-01-201731. ISSN 1528-0020. PMC 2780305. PMID 19745070.
↑ Bracht, Jillian Wilhelmina Paulina; et al. (2019). "BRAF Mutations Classes I, II, and III in NSCLC Patients Included in the SLLIP Trial: The Need for a New Pre-Clinical Treatment Rationale". Cancers. 11 (9). doi:10.3390/cancers11091381. ISSN 2072-6694. PMC 6770188. PMID 31533235.
↑ ^9.0 ^9.1 Durham, Benjamin H.; et al. (2017). "Genomic analysis of hairy cell leukemia identifies novel recurrent genetic alterations". Blood. 130 (14): 1644–1648. doi:10.1182/blood-2017-01-765107. ISSN 1528-0020. PMC 5630011. PMID 28801450.
↑ ^10.0 ^10.1 A, Nordgren; et al. (2010). "Characterisation of Hairy Cell Leukaemia by Tiling Resolution Array-Based Comparative Genome Hybridisation: A Series of 13 Cases and Review of the Literature". PMID 19682064.
↑ Zhang, Rui; et al. (2020). "Difference of genomic copy numbers alterations between hairy cell leukemia-variant and classical hairy cell leukemia: a pilot retrospective study in Chinese". International Journal of Medical Sciences. 17 (3): 325–331. doi:10.7150/ijms.39307. ISSN 1449-1907. PMC 7053350 Check |pmc= value (help). PMID 32132867 Check |pmid= value (help).
↑ ^12.0 ^12.1 Arons, Evgeny; et al. (2011). "Molecular variant of hairy cell leukemia with poor prognosis". Leukemia & Lymphoma. 52 Suppl 2: 99–102. doi:10.3109/10428194.2011.565841. ISSN 1029-2403. PMID 21599610.
↑ ^13.0 ^13.1 Wang, Chunmei; et al. (2017). "Krüppel-like factor 2 suppresses human gastric tumorigenesis through inhibiting PTEN/AKT signaling". Oncotarget. 8 (59): 100358–100370. doi:10.18632/oncotarget.22229. ISSN 1949-2553. PMC 5725026. PMID 29245984.
↑ ^14.0 ^14.1 Tschernitz, Sebastian; et al. (2014). "Alternative BRAF mutations in BRAF V600E-negative hairy cell leukaemias". British Journal of Haematology. 165 (4): 529–533. doi:10.1111/bjh.12735. ISSN 1365-2141. PMID 24433452.
↑ ^15.0 ^15.1 Xi, Liqiang; et al. (2012). "Both variant and IGHV4-34-expressing hairy cell leukemia lack the BRAF V600E mutation". Blood. 119 (14): 3330–3332. doi:10.1182/blood-2011-09-379339. ISSN 1528-0020. PMC 3321859. PMID 22210875.
↑ ^16.0 ^16.1 Waterfall, Joshua J.; et al. (2014). "High prevalence of MAP2K1 mutations in variant and IGHV4-34-expressing hairy-cell leukemias". Nature Genetics. 46 (1): 8–10. doi:10.1038/ng.2828. ISSN 1546-1718. PMC 3905739. PMID 24241536.
↑ Ritterhouse, Lauren L.; et al. (2015). "BRAF V600E mutation-specific antibody: A review". Seminars in Diagnostic Pathology. 32 (5): 400–408. doi:10.1053/j.semdp.2015.02.010. ISSN 0740-2570. PMID 25744437.
↑ Loo, Eric; et al. (2018). "BRAF V600E Mutation Across Multiple Tumor Types: Correlation Between DNA-based Sequencing and Mutation-specific Immunohistochemistry". Applied immunohistochemistry & molecular morphology: AIMM. 26 (10): 709–713. doi:10.1097/PAI.0000000000000516. ISSN 1533-4058. PMID 29271794.
↑ Villemagne, Bruno; et al. (2005). "Two new cases of familial hairy cell leukemia associated with HLA haplotypes A2, B7, Bw4, Bw6". Leukemia & Lymphoma. 46 (2): 243–245. doi:10.1080/10428190400013589. ISSN 1042-8194. PMID 15621808.
↑ Casado, L. F.; et al. (1998). "Familial hairy cell leukemia: a HLA-linked disease or farmers-linked disease?". Haematologica. 83 (8): 751–752. ISSN 0390-6078. PMID 9793263.

Notes

*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. *Citation of this Page: “Hairy cell leukaemia”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 09/6/2024, https://ccga.io/index.php/HAEM5:Hairy_cell_leukaemia.

[:1-1] 1.0 ^1.1 ^1.2 ^1.3 ^1.4 ^1.5 ^1.6 ^1.7 Maitre, Elsa; et al. (2019). "Hairy cell leukemia: 2020 update on diagnosis, risk stratification, and treatment". American Journal of Hematology. 94 (12): 1413–1422. doi:10.1002/ajh.25653. ISSN 1096-8652. PMID 31591741.

[2] Lr, Teras; et al. (2016). "2016 US Lymphoid Malignancy Statistics by World Health Organization Subtypes". PMID 27618563.

[:2-3] 3.0 ^3.1 ^3.2 ^3.3 Grever, Michael R.; et al. (2017). "Consensus guidelines for the diagnosis and management of patients with classic hairy cell leukemia". Blood. 129 (5): 553–560. doi:10.1182/blood-2016-01-689422. ISSN 0006-4971. PMC 5290982. PMID 27903528.CS1 maint: PMC format (link)

[:3-4] 4.0 ^4.1 ^4.2 ^4.3 Thompson, Ella R.; et al. (2020). "Detection of an IGH-BRAF fusion in a patient with BRAF Val600Glu negative hairy cell leukemia". Leukemia & Lymphoma: 1–3. doi:10.1080/10428194.2020.1753045. ISSN 1029-2403. PMID 32319330 Check |pmid= value (help).

[:4-5] 5.0 ^5.1 ^5.2 ^5.3 Rahman, Zaid Abdel; et al. (2020). "Hairy cell leukemia with CCND1/IGH fusion gene and BRAF V600E mutation". Leukemia Research Reports. 13: 100197. doi:10.1016/j.lrr.2020.100197. ISSN 2213-0489. PMC 7096740 Check |pmc= value (help). PMID 32257795 Check |pmid= value (help).

[6] National Comprehensive Cancer Network (January 2020). "NCCN Clinical Practice Guidelines in Oncology: Hairy Cell Leukemia" (PDF).CS1 maint: display-authors (link)

[:0-7] 7.0 ^7.1 ^7.2 ^7.3 Arons, Evgeny; et al. (2009). "VH4-34+ hairy cell leukemia, a new variant with poor prognosis despite standard therapy". Blood. 114 (21): 4687–4695. doi:10.1182/blood-2009-01-201731. ISSN 1528-0020. PMC 2780305. PMID 19745070.

[8] Bracht, Jillian Wilhelmina Paulina; et al. (2019). "BRAF Mutations Classes I, II, and III in NSCLC Patients Included in the SLLIP Trial: The Need for a New Pre-Clinical Treatment Rationale". Cancers. 11 (9). doi:10.3390/cancers11091381. ISSN 2072-6694. PMC 6770188. PMID 31533235.

[:5-9] 9.0 ^9.1 Durham, Benjamin H.; et al. (2017). "Genomic analysis of hairy cell leukemia identifies novel recurrent genetic alterations". Blood. 130 (14): 1644–1648. doi:10.1182/blood-2017-01-765107. ISSN 1528-0020. PMC 5630011. PMID 28801450.

[:6-10] 10.0 ^10.1 A, Nordgren; et al. (2010). "Characterisation of Hairy Cell Leukaemia by Tiling Resolution Array-Based Comparative Genome Hybridisation: A Series of 13 Cases and Review of the Literature". PMID 19682064.

[11] Zhang, Rui; et al. (2020). "Difference of genomic copy numbers alterations between hairy cell leukemia-variant and classical hairy cell leukemia: a pilot retrospective study in Chinese". International Journal of Medical Sciences. 17 (3): 325–331. doi:10.7150/ijms.39307. ISSN 1449-1907. PMC 7053350 Check |pmc= value (help). PMID 32132867 Check |pmid= value (help).

[:7-12] 12.0 ^12.1 Arons, Evgeny; et al. (2011). "Molecular variant of hairy cell leukemia with poor prognosis". Leukemia & Lymphoma. 52 Suppl 2: 99–102. doi:10.3109/10428194.2011.565841. ISSN 1029-2403. PMID 21599610.

[:8-13] 13.0 ^13.1 Wang, Chunmei; et al. (2017). "Krüppel-like factor 2 suppresses human gastric tumorigenesis through inhibiting PTEN/AKT signaling". Oncotarget. 8 (59): 100358–100370. doi:10.18632/oncotarget.22229. ISSN 1949-2553. PMC 5725026. PMID 29245984.

[:9-14] 14.0 ^14.1 Tschernitz, Sebastian; et al. (2014). "Alternative BRAF mutations in BRAF V600E-negative hairy cell leukaemias". British Journal of Haematology. 165 (4): 529–533. doi:10.1111/bjh.12735. ISSN 1365-2141. PMID 24433452.

[:10-15] 15.0 ^15.1 Xi, Liqiang; et al. (2012). "Both variant and IGHV4-34-expressing hairy cell leukemia lack the BRAF V600E mutation". Blood. 119 (14): 3330–3332. doi:10.1182/blood-2011-09-379339. ISSN 1528-0020. PMC 3321859. PMID 22210875.

[:11-16] 16.0 ^16.1 Waterfall, Joshua J.; et al. (2014). "High prevalence of MAP2K1 mutations in variant and IGHV4-34-expressing hairy-cell leukemias". Nature Genetics. 46 (1): 8–10. doi:10.1038/ng.2828. ISSN 1546-1718. PMC 3905739. PMID 24241536.

[17] Ritterhouse, Lauren L.; et al. (2015). "BRAF V600E mutation-specific antibody: A review". Seminars in Diagnostic Pathology. 32 (5): 400–408. doi:10.1053/j.semdp.2015.02.010. ISSN 0740-2570. PMID 25744437.

[18] Loo, Eric; et al. (2018). "BRAF V600E Mutation Across Multiple Tumor Types: Correlation Between DNA-based Sequencing and Mutation-specific Immunohistochemistry". Applied immunohistochemistry & molecular morphology: AIMM. 26 (10): 709–713. doi:10.1097/PAI.0000000000000516. ISSN 1533-4058. PMID 29271794.

[19] Villemagne, Bruno; et al. (2005). "Two new cases of familial hairy cell leukemia associated with HLA haplotypes A2, B7, Bw4, Bw6". Leukemia & Lymphoma. 46 (2): 243–245. doi:10.1080/10428190400013589. ISSN 1042-8194. PMID 15621808.

[20] Casado, L. F.; et al. (1998). "Familial hairy cell leukemia: a HLA-linked disease or farmers-linked disease?". Haematologica. 83 (8): 751–752. ISSN 0390-6078. PMID 9793263.

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