Acute Monoblastic and Monocytic Leukemia

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Primary Author(s)*

Fei Yang, MD, FACMG
Oregon Health & Science University, Portland, OR

Cancer Category/Type

Acute Myeloid Leukemia

Cancer Sub-Classification / Subtype

Acute monoblastic and monocytic leukemia

Definition / Description of Disease

Acute monoblastic and monocytic leukemia are myeloid leukemias in which the peripheral blood or bone marrow has ≥20% blasts (including promonocytes) and in which ≥80% of the leukemic cells are of monocytic lineage (monoblasts, promonocytes and monocytes). Neutrophils may be noted (<20%). In acute monoblastic leukemia, most (≥80%) of the monocytic cells are monoblasts; while in acute monocytic leukemia, most of the monocytic cells are promonocytes or monocytes. In the 2016 revision to the World Health Organization (WHO) classification system, acute monoblastic and monocytic leukemia is a distinct entity within the section of Acute Myeloid Leukemia (AML), Not Otherwise Specified[1][2]. This entity does not meet the criteria for inclusion in any of the other AML groups (i.e. AML with Recurrent Genetic Abnormalities, AML with Myelodysplasia-Related Changes, or Therapy-Related Myeloid Neoplasms).

Synonyms / Terminology

Acute monoblastic leukemia; acute monocytic leukemia; French-American-British (FAB) classification M5, Monoblastic leukemia NOS

Epidemiology / Prevalence

Acute monoblastic leukemia:

  • less than 5% of AML cases
  • more common in young individuals

Acute monocytic leukemia:

  • less than 5% of AML cases
  • more common in adults; the median patient age is 49 years
  • the male-to-female ratio is 1.8:1

Clinical Features

  • Common manifestations include extramedullary masses, lymphadenopathy, cutaneous and gingival infiltration, CNS involvement and presenting with bleeding disorders[2]
  • May present with acute respiratory failure[3]

Sites of Involvement

Bone marrow; extramedullary sites such as lymph nodes, skin, gingiva, and CNS.

Morphologic Features

  • Monoblasts are large cells with abundant cytoplasm, which can be moderately to intensely basophillic, and round nuclei with delicate lacy chromatin and one or more predominant nucleoli; scattered azurophillic granuoles and vacuoles may be present.
  • Promonocytes have a more irregular and delicately convoluted nuclear configuration and cytoplasm which is usually less basophillic and more granulated.
  • Hemophagocytosis (erythrophagocytosis) may be observed, often associated with t(8;16)(p11.2;p13.3).
  • The extramedullary lesion may be composed mainly of monoblasts, promocytes or both.

Immunophenotype

Cytochemistry

  • Monoblast granules and monocytes are strongly positive for non-specific esterase and lysozyme in most cases
  • Monoblasts are typically negative for myeloperoxidase (MPO), although promonocytes may have scattered positivity.

Often a complex immunophenotype with multiple blast populations including:

  • immature blasts with CD34 (30% of cases) and/or KIT (CD117) expression
  • populations with myeloid markers: CD13, CD33, CD15, CD65
  • populations with at least two monocytic markers: CD4, CD14, CD11b, CD11c, CD64, CD36, CD68, and lysozyme
  • most cases are positive for HLA-DR
  • MPO can be expressed in acute monocytic leukemia and less often in monoblastic leukemia
Finding Marker
Positive (universal) EXAMPLE CD1
Positive (subset) EXAMPLE CD2
Negative (universal) EXAMPLE CD3
Negative (subset) EXAMPLE CD4

Chromosomal Rearrangements (Gene Fusions)

Chromosomal Rearrangement Genes in Fusion (5’ or 3’ Segments) Pathogenic Derivative Prevalence
t(8;16)(p11.2;p13.3) 5'KAT6A / 3'CREBBP or 5'CREBBP / 3'KAT6A der(8) or der(16) 0.2% of AML

Characteristic Chromosomal Aberrations / Patterns

Myeloid-associated nonspecific cytogenetic abnormalities are present in most cases.

Genomic Gain/Loss/LOH

Put your text here and/or fill in the table

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)

Put your text here and/or fill in the tables

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

Type Gene/Region/Other
Concomitant Mutations EXAMPLE IDH1 R123H
Secondary Mutations EXAMPLE Trisomy 7
Mutually Exclusive EXAMPLE EGFR Amplification

Epigenomics (Methylation)

None

Genes and Main Pathways Involved

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Diagnostic Testing Methods

  • Conventional chromosome analysis
  • FISH myeloid panel
  • FISH or RT-PCR for KAT6A-CREBBP gene rearrangement

Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)

Diagnosis

  • The main differential diagnoses of acute monoblastic leukemia include: AML without maturation, AML with minimal differentiation, AML with t(9;11)(p21.3;q23.3), and acute megakaryoblastic leukemia (AMKL)[2]. Extramedullary monoblastic sarcoma needs to be differentiated from malignant lymphoma or soft tissue sarcomas[2].
  • The main differential diagnoses of acute monocytic leukemia include: chronic myelomonocytic leukemia, acute myelomonocytic leukemia, and microgranular acute promyelocytic leukamia (APL)[2].
  • Haemophagocytosis (erythrophagocytosis) with t(8;16)(p11.2;p13.3) may also occur in acute myelomonocytic leukemia and some cases of AML with maturation[2].

Prognosis

  • Multiple studies have shown that t(8;16)(p11.2;p13.3) positive AML usually has a poor prognosis[4][5].

Familial Forms

Put your text here

Other Information

Put your text here

Links

http://atlasgeneticsoncology.org/Anomalies/t0816ID1018.html

References

  1. 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. World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. IARC Press: Lyon, France, p160-161.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 Arber, Daniel A.; et al. (2016). "The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia". Blood. 127 (20): 2391–2405. doi:10.1182/blood-2016-03-643544. ISSN 1528-0020. PMID 27069254.
  3. Azoulay, Elie; et al. (2003). "Acute monocytic leukemia presenting as acute respiratory failure". American Journal of Respiratory and Critical Care Medicine. 167 (10): 1329–1333. doi:10.1164/rccm.200206-554OC. ISSN 1073-449X. PMID 12574074.
  4. Heim, S.; et al. (1987). "A new specific chromosomal rearrangement, t(8;16) (p11;p13), in acute monocytic leukaemia". British Journal of Haematology. 66 (3): 323–326. doi:10.1111/j.1365-2141.1987.tb06917.x. ISSN 0007-1048. PMID 3476150.
  5. Haferlach, T.; et al. (2009). "AML with translocation t(8;16)(p11;p13) demonstrates unique cytomorphological, cytogenetic, molecular and prognostic features". Leukemia. 23 (5): 934–943. doi:10.1038/leu.2008.388. ISSN 1476-5551. PMID 19194466.

Notes

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