Acute myeloid leukemia

Acute myeloid leukemia (AML) is a disease that is characterized by uncontrolled proliferation of clonal neoplastic cells and accumulation in the bone marrow of blasts with an impaired differentiation program. AML accounts for approximately 80% of all adult leukemias and remains the most common cause of leukemia death. Two major types of genetic events have been described that are crucial for leukemic transformation. A proposed necessary first event is disordered cell growth and upregulation of cell survival genes. The most common of these activating events were observed in the RTK Flt3, in N-Ras and K-Ras, in Kit, and sporadically in other RTKs. Alterations in myeloid transcription factors governing hematopoietic differentiation provide second necessary event for leukemogenesis. Transcription factor fusion proteins such as AML-ETO, PML-RARalpha or PLZF-RARalpha block myeloid cell differentiation by repressing target genes. In other cases,  the transcription factors themselves are mutated.

Human Diseases; Cancers

PMID:16236521

Steffen B, Muller-Tidow C, Schwable J, Berdel WE, Serve H.

The molecular pathogenesis of acute myeloid leukemia.

Crit Rev Oncol Hematol 56:195-221 (2005)

PMID:12563308

Tenen DG.

Disruption of differentiation in human cancer: AML shows the way.

Nat Rev Cancer 3:89-101 (2003)

PMID:16146838

Choudhary C, Muller-Tidow C, Berdel WE, Serve H.

Signal transduction of oncogenic Flt3.

Int J Hematol 82:93-9 (2005)

PMID:12951584

Stirewalt DL, Radich JP.

The role of FLT3 in haematopoietic malignancies.

Nat Rev Cancer 3:650-65 (2003)

PMID:16642045

Martelli AM, Nyakern M, Tabellini G, Bortul R, Tazzari PL, Evangelisti C, Cocco L.

Phosphoinositide 3-kinase/Akt signaling pathway and its therapeutical implications for human acute myeloid leukemia.

Leukemia 20:911-28 (2006)

PMID:15625120

Lennartsson J, Jelacic T, Linnekin D, Shivakrupa R.

Normal and oncogenic forms of the receptor tyrosine kinase kit.

Stem Cells 23:16-43 (2005)

PMID:11721960

Lorsbach RB, Downing JR.

The role of the AML1 transcription factor in leukemogenesis.

Int J Hematol 74:258-65 (2001)

PMID:12468433

Mizuki M, Schwable J, Steur C, Choudhary C, Agrawal S, Sargin B, Steffen B, Matsumura I, Kanakura Y, Bohmer FD, Muller-Tidow C, Berdel WE, Serve H.

Suppression of myeloid transcription factors and induction of STAT response genes by AML-specific Flt3 mutations.

Blood 101:3164-73 (2003)

PMID:17554387

Mikesch JH, Steffen B, Berdel WE, Serve H, Muller-Tidow C.

The emerging role of Wnt signaling in the pathogenesis of acute myeloid leukemia.

Leukemia : (2007)

PMID:16352814

Mueller BU, Pabst T, Fos J, Petkovic V, Fey MF, Asou N, Buergi U, Tenen DG.

ATRA resolves the differentiation block in t(15;17) acute myeloid leukemia by restoring PU.1 expression.

Blood 107:3330-8 (2006)