Acute Megakaryoblastic Leukaemia (AMKL)

Acute megakaryoblastic leukaemia (AMKL) is a rare subtype of acute myeloid leukaemia (AML). It is more common in children than in adults. In children with Down syndrome, AMKL is the most common type of AML.

AMKL is included under three subtypes of AML:

  1. AMKL with chromosome t(1;22)(p13;q13) with gene RBM15-MKL1
  2. Myeloid proliferations related to Down syndrome: increase in bone marrow cells, usually megakaryoblasts
    1. Transient myeloproliferative disorder: transient abnormal increase of all bone marrow cells
    1. Myeloid leukaemia associated with Down syndrome
  3. AMKL, not otherwise specified (NOS)

AMKL can occur for the following reasons:

  • As a new disease
  • Due to a ‘secondary effect’ of previous chemotherapy treatment
  • As a progression from myeloproliferative cancer or myelodysplastic syndrome

What are the symptoms of AMKL?

Patients with AMKL may be affected in several different ways and may develop one or more of the following disease features:

  • Anaemia
  • Bleeding or bruising due to thrombocytopenia (low platelet count)
  • Increased susceptibility to infections
  • Enlarged organs, mainly the liver and spleen
  • Bone lesions
  • Leukocytosis (increase in the number of white cells in the blood)
  • Myelofibrosis (formation of fibrous tissue within the bone marrow that disrupts blood cell production)

How is AMKL diagnosed?

The diagnostic criteria for AMKL is a proliferation of 20% or more of megakaryoblasts and 50% or more of blasts of megakaryocytic lineage as seen from bone marrow aspirates or peripheral blood.

  • Peripheral blood – blood may contain megakaryoblastic fragments and small blast cells which tend to have variable shapes.
  • Bone marrow aspirate and biopsy – bone marrow biopsies can show numerous blasts, clusters of micro-megakaryoblasts or more mature megakaryoblasts. There is a corresponding decrease in usual bone marrow maturation. Cytoplasmic blebs may also be identified to help with the diagnosis.

Further evidence to confirm the diagnosis can also come from the following tests:

  • Flow cytometry – this identifies the specific antigens by separating the different types from blood or bone marrow, and then counting them.
  • Immunophenotyping – this test uses antibodies to identify the types of antigens or markers on the surface of the cells. For AMKL, the cells normally show positivity for CD33, CD13, CD41, CD42, CD61 and factor VIII, and negativity for myeloperoxidase.
  • Chromosome analysis based on the patient group affected by AMKL.

Children with AMKL

Population characteristics

  • Occurs in children younger than three years of age with Down syndrome.
  • Occurs more commonly in females.


  • Translocation of chromosome t(1;22)(p13;q13) and gene RBM15-MKL1: A chromosome translocation is the transfer of one part of a chromosome to another part of the same or a different chromosome, resulting in the rearrangement of the genes.
  • AMKL, NOS: This subtype includes chromosome abnormalities other than those that feature in other subtypes.


Despite recent improvements in the understanding of the causes of AMKL, the optimal treatment is still debated. Currently there is no ‘targeted therapy’ available for AMKL.

Some haematologists treat children with AMKL but without Down syndrome as very high-risk and recommend an allogeneic stem cell transplant as soon as complete remission has been achieved. However, others treat these children with intensive chemotherapy only, and have achieved excellent survival rates.

Nevertheless, treatment protocols nearly always include cytarabine and an anthracycline; originally produced as an antibiotic.


The prognosis for children with AMKL but not Down syndrome is controversial. Although, the prognosis tends to be worse than for other forms of AMKL.

Prognostic factors can include:

  • The gene inv(16) CBFA2T3-GLIS2 – patients with this gene are predicted a poor outcome.
  • The t(1;22) translocation – as long as intensive chemotherapy and adequate supportive care is provided, patients could have a favourable prognosis.

AMKL patients with Down syndrome

Patient characteristics

Transient myeloproliferative disorder:

  • This is a temporary abnormal increase of all bone marrow cells within a few days of birth, and usually resolves within one to two months. It is found in 10% of newborn infants with Down syndrome.
  • Up to 20% of children with this disorder go on to develop AMKL within the first four years of life.


Myeloid leukaemia associated with Down syndrome:

  • Occurs usually in the first four years of life.
  • Average age of diagnosis is 1.8 years.
  • White cell counts are often lower.


Transient myeloproliferative disorder:

  • The causes are not fully understood; however, it is thought to be involved with Down syndrome.

Myeloid leukaemia associated with Down syndrome:

  • Children with Down syndrome have the chromosome abnormality trisomy 21 which is thought to be directly related to the cancerous transformation of haematopoietic cells, including megakaryocytes.
  • Along with this, nearly all children with myeloid leukaemia associated with Down syndrome have a GATA1 mutation.


Transient myeloproliferative disorder:

  • Treatment with low dose cytarabine for three to 12 days.
  • However, it is still unclear whether the treatment of transient myeloproliferative disorder will alter the risk of developing AMKL.

Myeloid leukaemia associated with Down syndrome:

  • Children with Down syndrome are seen to achieve better results with intensive chemotherapy; however, they are more susceptible to the toxic side effects of the chemotherapy.
  • Very good results have been achieved using dose-reduced treatment protocols.


Overall, patients with AMKL associated with Down syndrome have an excellent prognosis with a greater than 90% overall survival rate.

Adults with AMKL

Patient characteristics

  • AMKL in adults occurs in only 1% of all AML cases.
  • Median age of adults with AMKL is 56 years (based on a study of 37 patients who ranged between 21 and 78 years).


  • The genetic basis for adults with AMKL is poorly defined given the rarity of the disease.
  • AMKL in adults occurs as part of the AMKL, NOS subtype, which includes chromosome abnormalities other than those featured in other subtypes.
  • AMKL may also progress from myeloproliferative cancer or myelodysplastic syndrome.


Intensive chemotherapy is a necessity for adults with AMKL but not Down syndrome because they have a poor prognosis.


From the limited experience of AMKL in adults, a poor prognosis, despite treatment with intensive chemotherapy, can be expected but there is still room for hope.

Although the overall survival rate is around four to ten months, complete remission is achieved in around half of adult AMKL patients.

Questions to ask your doctor

Questions to ask your doctor about AMKL

We understand going through a blood cancer journey can be difficult. It may help to talk to a close friend or relative about how you are feeling. Here are some questions that may be useful to ask your doctor.

  • How would I know if I had AMKL?
  • What tests will I need to have?
  • What will the tests show?
  • How long will the results take?
  • How rare is AMKL?
  • What sort of treatment will I need?
  • How long will my treatment last?
  • What will the side effects be?
  • Is there anything I should or shouldn’t eat?
  • Will I be able to go back to work?
  • Where can I get help with claiming benefits and grants?
  • Where can I get help dealing with my feelings?

Further information

We have free patient information available for AMKL patients.

You can download or order physical copies through our shop.

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Publication date: March 2019 Review date: March 2022