Difference between revisions of "Acute Erythroid Leukemia"

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Latest revision as of 13:45, 12 December 2023

Primary Author(s)*

Ashwini Yenamandra PhD FACMG

Cancer Category/Type

Acute Myeloid Leukemia

Cancer Sub-Classification / Subtype

In the 2008 WHO classification, Acute Erythroid leukemia (AEL) was classified into two subtypes: Erythroleukemia (erythroid/myeloid) and Pure Erythroid Leukemia (PEL). However, in the 2016 WHO update, Erythroleukemia was merged into myelodysplastic syndrome, while PEL is now the only type of AEL [1-12].

Definition / Description of Disease

PEL is a rare form of acute leukemia with an aggressive clinical course and is characterized by an uncontrolled proliferation of immature erythroid precursors (proerythroblastic or undifferentiated) [1-12]. Erythroleukemia (erythroid/myeloid) may be de novo or evolved from myeloid or sometimes from myeloproliferative neoplasms (MPN) [1,10].

Links

HAEM5:Acute erythroid leukaemia

References

1. Arber DA, et al., (2008). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, Editors. IARC Press: Lyon, France, p135-136.

2. Shaowei Qiu, et al., (2017). An analysis of 97 previously diagnosed de novo adult acute erythroid leukemia patients following the 2016 revision to World Health Organization classification. BMC Cancer 17: 544, PMID 28793875.

3. Zhuang Zuo, et al., (2010). Acute Erythroid Leukemia (Review Article). Arch Pathol Lab Med 134:1261-1270, PMID 20807044.

4. Arber DA, et al., (2016). The updated WHO classification of Hematological malignancies. The 2016 revision to the World Health organization classification of myeloid neoplasms and acute leukemia (Review Series). Blood 127(20):2391-2405, PMID 27069254.

5. Zuo Z, et al., (2012). Acute myeloid leukemia (AML) with erythroid predominance exhibits clinical and molecular characteristics that differ from other types of AML. PLoS One 7(7):e41485, PMID 22844482.

6. Grossmann V, et al., (2013). Acute erythroid leukemia (AEL) can be separated into distinct prognostic subsets based on cytogenetic and molecular genetic characteristics. Leukemia 27(9): 1940-1943, PMID 23648669.

7. Porwit A, et al., (2011). Acute myeloid leukemia with expanded erythropoiesis. Haematologica 96(9):1241-1243, PMID 21880638.

8. Hasserjian RP, et al., (2010). Acute erythroid leukemia: a reassessment using criteria refined in the 2008 WHO classification. Blood 115(10):1985-1992, PMID 20040759.

9. Wang SA, et al., (2015). Acute erythroleukemias, acute megakaryoblastic leukemias, and reactive mimics: a guide to a number of perplexing entities. Am J Clin Pathol 144(1):44-60, PMID 26071461.

10. Wang W, et al., (2016). Acute Erythroid Leukemia. Am J Hematol. 2017; 92:292–296, PMID 2800685.

11. Yenamandra A, et al., (2016). Acute Erythroblastic Leukemia (AEL): A rare subset of de novo AML with a complex rearrangement involving ETV6 locus and loss of RB1 locus. Int Clin Pathol J 2(2): 00032, DOI: 10.15406/icpjl.2016.02.00032.

12. Fauzia SF, et al., (2017). Pure erythroid leukemia: The sole acute erythroid leukemia. Int J Bone Marrow Res 1: 001-05 (open access).

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.

@@ Line 1: / Line 1: @@
-{{Under Construction}}
 ==Primary Author(s)*==
 Ashwini Yenamandra PhD FACMG
 __TOC__
@@ Line 9: / Line 7: @@
 ==Cancer Category/Type==
-'''Acute Myeloid Leukemia'''
+[[AML|Acute Myeloid Leukemia]]
 ==Cancer Sub-Classification / Subtype==
-'''Pure Erythroid Leukemia (PEL) is the only subtype in Acute Erythroid Leukemia (AEL).'''
+In the 2008 WHO classification, Acute Erythroid leukemia (AEL) was classified into two subtypes: Erythroleukemia (erythroid/myeloid) and Pure Erythroid Leukemia (PEL). However, in the 2016 WHO update, Erythroleukemia was merged into myelodysplastic syndrome, while PEL is now the only type of AEL [1-12].
 ==Definition / Description of Disease==
-'''In the 2008 WHO classification Acute Erythroid leukemia (AEL) was classified into two subtypes, one subtype was Erythroleukemia and second subtype was pure erythroid leukemia (PEL).
+PEL is a rare form of acute leukemia with an aggressive clinical course and is characterized by an uncontrolled proliferation of immature erythroid precursors (proerythroblastic or undifferentiated) [1-12].  Erythroleukemia (erythroid/myeloid) may be de novo or evolved from myeloid or sometimes from myeloproliferative neoplasms (MPN) [1,10].
-'''However, in the 2016 WHO update, erythroleukemia was merged into myelodysplastic syndrome, and PEL was described as the only subtype of AEL [1-12]
-'''PEL is a rare form of acute leukemia with an aggressive clinical course and is characterized by an uncontrolled proliferation of immature erythroid precursors (proerythroblastic or undifferentiated) [1-12].
-''''''
-'''
-==Synonyms / Terminology==
-Also known as AML-M6b and Di Guglielmo syndrome due to the recognition of the work of Di Guglielmo. [1, 2].
-==Epidemiology / Prevalence==
-PEL is extremely rare with a small number of reported cases, accounting for 3-5% of AML cases [1, 2, 10]. Median survival is usually three months [12].
-==Clinical Features==
-PEL has an aggressive clinical course with neoplastic proliferation of immature erythroid precursor (proerythroblastic or undifferentiated) cells. Average survival rate is three months [1, 10]. PEL is characterized by neoplastic proliferation composed of >80% immature erythroid precursors of which proerythroblast constitute ≥30%. [12].
-Clinical features include profound anemia, circulating erythroblasts, pancytopenia, extensive bone marrow involvement, fatigue, infections, weight loss, fever, night sweats, hemoglobin level under 10.0 g/dL, thrombocytopenia [1, 10]. Erythroleukemia (erythroid/myeloid) may be de novo or evolved from myeloid or sometimes from myeloproliferative neoplasms (MPN). [1,10].
-==Sites of Involvement==
-Bone marrow, Blood
-==Morphologic Features==
-PEL is characterized by medium to large erythroblasts with round nuclei, fine chromatin and one or more nucleoli (proerythroblast). Cytoplasm is deeply basophilic, often granular with demarcated vacuoles and are often Periodic-Acid-Schiff stain (PAS) positive. Blasts can be small and may resemble lymphoblasts[1]. Cells are usually negative for Myeloperoxidase (MPO) and Sudan Black (SBB).  Bone marrow biopsy may have undifferentiated cells [1].
-[[File:pic-2.png|options|caption]]
-==Immunophenotype==
-Differentiated PEL may express Glycophorin and hemoglobin A, absence of myeloperoxidase (MPO) and other myeloid markers [1], Blasts are negative for HLA-Dr, CD34, positive for CD117[1]
-Immature forms can be negative for Glycophorin or weekly expressed. Positive for Carbonic anhydrase 1, Gero antobody against the Gerbich blood group or CD36 especially at earlier stages of differentiation. CD41 and CD61 are negative [1, 12].
-{| class="wikitable sortable"
-|-
-! Finding   !! Marker
-|-
-|Positive (universal) || Hemoglobin A, Glycophorin A, Spectrin, ABH blood group antigens, and HLA-DR
-|-
-|Positive (subset) || CD13, CD33, CD34, CD117 (KIT), and MPO, Gerbich blood group (Gero) antibody, carbonic anhydrase 1, and CD36, CD41 and CD61
-|-
-|Negative (universal) || Myeloid-associated markers such as MPO,CD13,CD33,CD61, B and T Cell markers -CD10, CD19, CD79a, CD2, CD3, CD5,  monocytic markers CD11c CD14
-Megakaryoblastic markers: CD61, Others: CD34, anti-kappa, anti-lambda, CD45
-|-
-|Negative (subset) || HLA-DR, CD34, Glycophorin A
-|}
-==Chromosomal Rearrangements (Gene Fusions)==
-The genetic abnormalities that have been identified in PEL are similar to that of AML and MDS and consists of complex chromosomal abnormalities including -5/del(5q, -7/del(7q), +8 and/or RUNX1 and TP53 mutations [1 and AY].]. Rearrangement of NFIA-CBFA2T3 with t(1;16)(p31;q24) and MYND8-RELA with t(11;20)(p11;q11) have been reported in rare cases [10].
-A complex karyotype with 46,XY,der(5)del(5) (p15.1p15.1)t(5;12;7) (p15.1;p13;q32), der(7)t(5;12;7), der(12) del(12)(p13p13)t(5;12;7),del(13)(q12q14) was reported in a two year old boy with PEL [11]
-[[File:pic-3.png|options|caption]]
-{| class="wikitable sortable"
-|-
-! Chromosomal Rearrangement !! Genes in Fusion (5’ or 3’ Segments) !! Pathogenic Derivative !! Prevalence
-|-
-|t(1;16)(p31;q24) || 5’NFIA-/ 3’CBFA2T3  || der(16) || Rare
-|-
-|t(11;20)(p11;q11) || 5’MYND8/ 3’RELA ||  der(11) || Rare
-|}
-==Characteristic Chromosomal Aberrations / Patterns==
-JAK2, FLT3, RAS, NPM1, and CEBPA mutations have been reported to be rare in PEL [10-12].
-==Genomic Gain/Loss/LOH==
-Not Applicable
-{| class="wikitable sortable"
-|-
-! Chromosome Number !! Gain/Loss/Amp/LOH !! Region
-|-
-|EXAMPLE 8 || EXAMPLE Gain || EXAMPLE chr8:0-1000000
-|-
-|EXAMPLE 7 || EXAMPLE Loss || EXAMPLE chr7:0-1000000
-|}
-==Gene Mutations (SNV/INDEL)==
-Intraclonal heterogeneity and founder mutations of TP53 were reported in 92% (11 out of 12 cases) while  co-occurrence of TP53 mutation and deletion due to chromosome 17p abnormalities were detected in 73% of PEL cases [13].
-{| 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)==
-Not Applicable
-==Genes and Main Pathways Involved==
-The molecular mechanism is not completely understood.
-==Diagnostic Testing Methods==
-Morphology and IHC.
-==Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)==
-PEL has rapid and aggressive clinical course. Patients with PEL are treated similar to other types of AML. Stem cell transplantation (SCT) may have an improvement in the outcome of the disease. No therapeutic agents for specific target pathways are currently available [3].
-==Familial Forms==
-Not Applicable
-==Other Information==
-'''Differential Diagnosis''': PEL without morphological differentiation of erythroid maturation can be difficult to distinguish from megakaryoblastic leukemia (AML), ALL or lymphoma. The erythroid precursor immunophenotype helps in the diagnosis. Some cases can be complex with concurrent erythroid megakaryocytic involvement [1].
 ==Links==
-Put your links here
+*[[HAEM5:Acute erythroid leukaemia]]
 ==References==
-. Arber DA, et al., (2008). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4thedition.Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, Editors. IARC Press: Lyon, France, p135-136.
+. Arber DA, et al., (2008). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, Editors. IARC Press: Lyon, France, p135-136.
 . Shaowei Qiu, et al., (2017). An analysis of 97 previously diagnosed de novo adult acute erythroid leukemia patients following the 2016 revision to World Health Organization classification. BMC Cancer 17: 544, PMID 28793875.
@@ Line 174: / Line 43: @@
 . Wang W, et al., (2016). Acute Erythroid Leukemia. Am J Hematol. 2017; 92:292–296, PMID 2800685.
-. Yenamandra A, et al., (2016). Acute Erythroblastic Leukemia (AEL): A Rare Subset of De Novo AML with A Complex Rearrangement Involving ETV6 Locus and Loss of RB1 Locus. Int Clin Pathol J 2(2): 00032, DOI: 10.15406/icpjl.2016.02.00032
+. Yenamandra A, et al., (2016). Acute Erythroblastic Leukemia (AEL): A rare subset of de novo AML with a complex rearrangement involving ETV6 locus and loss of RB1 locus. Int Clin Pathol J 2(2): 00032, DOI: 10.15406/icpjl.2016.02.00032.
-. Fauzia SF, et al., (2017). Pure erythroid leukemia: The sole acute erythroid leukemia. Int J Bone Marrow Res. 2017; 1: 001-05.
-.Guillermo MB, et al., (2017). More than 1 TP53 abnormality is a dominant characteristic of pure erythroid leukemia. Blood 129(18):2384-2387, PMID: 28246192.
+. Fauzia SF, et al., (2017). Pure erythroid leukemia: The sole acute erythroid leukemia. Int J Bone Marrow Res 1: 001-05 (open access).
-== Notes ==
+==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.