What is Mixed Phenotype Acute Leukemia (MPAL)?

Mixed phenotype acute leukemia has qualities of both lymphoid and myeloid leukemias. These mixed qualities make it very difficult to diagnose and treat. The outlook for people with this type of leukemia is poorer than for those with other acute leukemias.

Acute leukemias typically develop in one of two cell lineages, lymphoid or myeloid. There’s another type of leukemia, called mixed phenotype acute leukemia (MPAL), that has markers from both lineages.

MPAL isn’t common. It only makes up about 1% to 3% of all acute adult leukemias and less than 5% of all acute pediatric leukemias.

Keep reading to learn more about MPAL, its symptoms, and how it’s diagnosed and treated. We also cover the outlook for people with MPAL and whether this type of leukemia is curable.

Acute leukemias are typically either lymphoid or myeloid in lineage. For example, there are:

• Acute lymphocytic leukemia (ALL): This type involves lymphoid cells that will eventually become white blood cells like B cells or T cells.
• Acute myeloid leukemia (AML): This type involves myeloid cells that will eventually become white blood cells like neutrophils or monocytes.

MPAL is a type of leukemia that has markers for both lymphoid and myeloid lineages. There are two general types of MPAL:

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• Bilineal: Bilineal means “two lineages.” In this type of MPAL, there are two separate populations of leukemia cells. One population is lymphoid, while the other is myeloid.
• Biphenotypic: Biphenotypic means “two types.” In this type of MPAL, there’s one population of leukemia cells. These cells express markers from both lymphoid and myeloid lineages.

The distinction between these two types of MPAL isn’t always so clear cut. For example, it’s possible for bilineal MPALs to transform into biphenotypic MPALs and vice versa.

The signs and symptoms of MPAL are similar to those of other acute leukemias. They may include:

• anemia, which can cause:
  • fatigue
  • weakness
  • dizziness or lightheadedness
  • shortness of breath

  Individuals with MPAL also typically have a high white blood cell count. Further, about 25% of people with MPAL have leukemia cells present in their central nervous system, which includes your brain and spinal cord.

  What exactly causes MPAL isn’t yet known. Generally speaking, leukemia happens when blood stem cells have genetic changes that cause them to grow and divide out of control.

  Certain genetic changes that affect your chromosomes are linked to MPAL:

  • Philadelphia chromosome: The Philadelphia chromosome is when parts of chromosome 9 and chromosome 22 swap places, leading to a fusion of the BCR and ABL1 genes on chromosome 22.
  • Chromosome 11q23 abnormalities: Chromosome 11q23 abnormalities involve alterations to a specific part of chromosome 11 called q23.

  Risk factors for MPAL

  MPAL is rare. As such, we still know little about specific risk factors. But research has found that MPAL is more common in people assigned male a birth.

  There are also differences in the ages of people who get bilineal versus biphenotypic MPAL. The median age to receive a diagnosis of bilineal MPAL is 18 years old. In contrast, the median age to receive a diagnosis of biphenotypic MPAL is 53 years old.

  Because MPAL is rare, it can be very difficult to diagnose. A doctor or healthcare professional will start by taking your medical history and doing a physical exam. They may order lab tests like:

  • complete blood count
  • peripheral blood smear
  • basic metabolic panel
  • coagulation tests

  If the results of these tests signal that you may have leukemia, a doctor will order a bone marrow aspiration and biopsy. The samples collected from this procedure can be used to look for and further characterize your leukemia cells.

  The diagnosis of MPAL involves carefully analyzing the bone marrow samples using immunotyping and chromosome analysis.

  Immunotyping looks at the different markers on your leukemia cells, typically using a process called flow cytometry. Chromosome analysis can look for changes like the Philadelphia chromosome or 11q23 abnormalities.

  MPAL can be classified into five different categories based off of immunotyping and chromosome analysis:

  • MPAL with t(9;22)(q34;q11.2); BCR-ABL1: People with this type of MPAL have the Philadelphia chromosome.
  • MPAL with t(v;11q23); KMT2A rearranged: Individuals with this type of MPAL have 11q23 abnormalities.
  • MPAL B-myeloid, NOS (not otherwise specified): Those with this type have MPAL with B-lymphoid and myeloid markers. They don’t have the Philadelphia chromosome or 11q23 abnormalities.
  • MPAL T-myeloid, NOS: Those with this type have MPAL with T-lymphoid and myeloid markers. They don’t have the Philadelphia chromosome or 11q23 abnormalities.
  • MPAL rare types: People who fall into this category have rarer types of MPAL.

  There are no established treatment guidelines for MPAL. Instead, the specific treatment of MPAL is based on the findings from immunotyping and chromosome analysis.

  Initial treatment typically involves chemotherapy, which uses drugs that disrupt the growth of leukemia cells. The chemotherapy regimen may be one that’s geared toward ALL, AML, or one that targets both ALL and AML.

  Individuals with the Philadelphia chromosome or 11q23 abnormalities will likely have a targeted therapy drug added to their initial treatment regimen. These drugs home in on certain markers linked to leukemia cells.

  Initial treatment may be followed by an allogenic stem cell transplant (SCT). The goal of an SCT is to create a healthy bone marrow that’s free of leukemia cells.

  In an allogeneic SCT, strong chemotherapy is used to kill the cells in your bone marrow, including the leukemia cells. You then receive an infusion of stem cells from a healthy matched donor.

  Is mixed phenotype acute leukemia (MPAL) curable?

  The mixed nature of MPAL makes it very challenging to treat. As such, the outlook for people with MPAL is generally poor.

  It’s possible that an SCT will provide a cure for some individuals. But many people with MPAL will experience a relapse of their leukemia at some point.