Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (333 page)

   IGH (14q32) rearrangements; most commonly t(8;14)(q24;q32) with MYC-IGH.

   Deletion/rearrangement of 9p (CDKN2A deletion); favorable prognosis in adults; possibly poor prognosis in children.

   Hyperdiploidy (54–58 chromosomes especially if associated with the combined trisomies of chromosomes 4 and 10 have the best prognosis).

   Hypodiploidy (the blasts contain <45 chromosomes, poor prognosis). Note that hyperdiploidy may represent doubling of a hypodiploid clone. This doubled clone still confers poor prognosis. High hyperdiploidy may also be seen in combination with BCR-ABL1 and with t(1;9) and also carries a poor prognosis.

   In addition to the genetic abnormalities demonstrated by chromosome and FISH studies, high-density single nucleotide polymorphism (SNP) arrays and gene expression profiles are being increasingly used to stratify patients and determine prognosis and therapeutic protocols.

   Once the initial profile of the leukemic cells had been established, the information is used to establish the effect of therapy as revealed by the presence of minimal residual disease (MRD), which correlates well with clinical outcome.

Additional Information

   CSF may show increased protein and cells, some recognizable as lymphoblasts. Because of high incidence of meningeal involvement, examination of CSF is part of all protocols.

   Serum LDH and sedimentation rate are elevated.

   Hypercalcemia, hyperpotassemia, hyperphosphatemia, and hyperuricemia may be present at diagnosis or develop as the result of therapy.

   Acute lysis syndrome may develop as the result of therapy.

Suggested Readings

Borowitz MJ, Chan JKC. B lymphoblastic leukaemia/lymphoma not otherwise specified. In:
WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues
, 4th ed. Lyon, France: International Agency for Research on Cancer; 2008:168–170.

Mullighan CG. The molecular genetic makeup of acute lymphoblastic leukemia.
Hematology Am Soc Hematol Educ Program.
2012;2012:389–396.

ACUTE MYELOID LEUKEMIA (AML)

   Definition

AML is a hematopoietic neoplasm involving a clonal proliferation of the myeloid line, involving granulocytic, or erythroid, or megakaryocytic hematopoietic stem cells. It is characterized by acquisition of somatic mutations that confer proliferative or survival advantage to the clonal cells and impair normal hematopoiesis. AML is a markedly heterogeneous disease with numerous genetic aberrations.

   Classification